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About Google Book Search Google's mission is to organize the world's information and to make it universally accessible and useful. Google Book Search helps rcaders discover the world's books while helping authors and publishers reach new audiences. You can search through the full icxi of this book on the web at |http : //books . google . com/| A TREATISE ON H^EMOPHILIA TREATISE ON H^MOPHILIA SOMETIMES CALI.ED THE HEREDITARY HMMORRHAGIC DIATHESIS BY J. WICKHAM LEGG, M.D. PASUALTY PHYSICIAN TO SAINT BARTHQLOMBW'S HOSPITAI« Omnia membra Etnisere simul rutilatum sanguine virus : Sanguis erant lacrimae: quaecumque foramina novit Hutnort ab his largus manat cruor : ora redundant Ut patulae nares : sudor rubet : omnia plenis Membra Jluunt venis; totum est prò vulnere corpus. Lucani Pharsalia, l^ìTh- LONDON H. K. LEWIS 136 GOWER STREET M DCCC LXXII /S7. /^- /(P^ PREFACE The foUowing pages bave been written for some time past : tbey were at first designed to form part of a larger work ; but they are now publisbed separately, as there exists no complete account of haemophilia in the English language. My attention was first drawn to tbis disease, nearly nine years ago, by seeing a boy, the subject of haemophilia, bleed to death of a simple epistaxis : since that time I bave made careful study of almost every case that has fallen under my observation ; and bave endeavoured, so far as my opportunities extended, to make myself acquainted with whatever has been written on tbis subject. I bave not attempted any new statistical observations : firstly, because ali deductions drawn from statistics based upon observa- tions which bave been contributed by different writers, are liable to grave error; and secondly, because the time seemed too vi PREFACE short, that has gone by since Lange published his careful researches, supplemented as they have been by those of Gran- didier in 1863, for much informatioq to be gained by a, new coUection of figures. London Jcmuary is^, 1872, TABLE OF CONTENTS CHAPTER I. InTRODUCTORY CONTAINING CaSES OF HìÈMOPHILIA . . 1 CHAPTER II. HlSTORY OF HiBMOPHILIA V ^7 CHAPTER HI. ìEtIOLOGY OF HiEMOPHÌLIA • 3^ CHAPTER IV. SyMPTOMS OF HiÈMOPHiLIA . .' . . . . • . 43 CHAPTER V. IdIOSYNCRASIES OF HiEMOPHILIA 73 CHAPTER VI. MORBID AnATOMY and PaTHOLOGY OF HiBMOPHILIA • • 77 CHAPTER VII. DlAGNOSlS AND pROGNOSIS OF H^MOPHILIA . . . IO3 CHAPTER Vm. Treatment of H^bmophilia iia CHAPTER IX. Hygiene and Social Relations of H^mophilia . . 124 CHAPTER X. On Certain H^morrhagic Diatheses in Women . .129 CHAPTER XI. LiTERATURE OF HiEMOPHILIA I38 ERRATUM. While the sixth chapter of this work was passing through the press, I received from Germany Schliemann's Wùrzburg dissertation, De dùposiiione ad haemorrhagtas perniciosas haereditaria, It was immediately apparent that the case, that I have quoted at p. 83 from Grandidier, as the report of Schlie- mann's post mortem examination of a Jew boy suffering from hsemophilia, is altogether worthless : from the clinical history of this patient, which is given at p. II of the dissertation, it is plain, to the most careless reader, that the patient, whose examination after death is recorded, was suffering from purpura, or the morbus maculosus Werlhofii^ as Schliemann himself remarks, and not from haemophilia of any degree. ADDENDUM. At the moment at which this work is published, an important observation has appeared in Lyon medicai for Dee. 24, 1871, on the post mortem examination of the joints in hsemophilia ; I can now do no more than point out to the student the existence of a great addition to our knowledge of the morbid anatomy of the joint swelling. TREATISE ON H.EMOPHILIA. CHAPTER I. Introductory. By Haemophilia is meant a disease, both hereditary and Chap. I. congenital ; usually lasting throughout the life of the patient ; accompanied by a haemorrhagic diathesis, and a tendency to swelling of the joints. The liability to abundant and long-continued bleed- ings is one of the chief symptoms of haemophilia. But the haemorrhages must not merely be obstinate and prolonged ; the tendency to bleed must be congenital, or almost congenital. It must not be assumed that every case, in which it is difficult to stop the flow of blood, is one of haemophilia. A tendency to great haemorrhage sometimes appears in the course of certain diseases, and may even last for years : but haemophilia is a disease which shows itself in infancy, and persists, as a rule, throughout the life of the patient. In England this disease is often called the haemor- rhagic diathesis, or tendency. I bave preferred to use the name haemophilia, because haemorrhagic diathesis has too wide a meaning. It would include ali diseases in which a haemorrhagic tendency is present ; and it is £tlso wanting in definition since it does not connote 6 INTRODUCTION. Chap. I. the hereditary and congenital character of the disease,- ^nor the tendency to sweUing of the joints ; this swelling of the joints is often a more marked feature in the disease than the bleeding. The tendency to haemor- rhage is only one symptom of this constitutional dis- order. - On the continent, the disease is universally called haemophilia,^ or haemorrhaphilia.* The former of these names is the more commonly used ; neither is good, but it is now too late to attempt to change. In Ger- many haemophiHa is also called Bluterkrankheit ; less commonly Blutsucht or Blutungssucht ; and individuai patients, Bluter^ a translation of the word bleeder^ used ^ The etymology of the word seems to be plain : af^a and (piXloL, M. de Fleury, however, prefers to derive the name from yXì3, a race, or tribe, with refer- ence, I suppose, to its hereditary character (Menu de la Soc, méd,- chir. de Bordeaux, t. i., p. 303.^ This derivation necessitates a change in the àccustomed man- ner of spelling : but ali the early German authors write the word hàmophilie : to which I have there- fore adhered. Various other names have been proposed : hsemorrhophilia, hae- matophilia, haemorrhag-ophilia, idiosyncrasia haemorrhagiqa, and morbus haematicus. A name pro- posed by Uhde (Deutsche Klinik, 1850, p. 539), is amychaemorrha- g-ia, from di^v^rj, a slight wound : perhaps it is the worst yet sug- gested. ^ Hsemorrhaphilia is the name used by Schònlein in his Vorles- ungen (third edit., 1837.) Vir- chow (Handb, d, spec, Path, und Ther, i. 264,^ seems to think that Schònlein was the author of the word haemophilia. I am unable to say from my own observation by what writer the name was first used. Die Hàmophilie is said to be the title of an inaugurai dissertati on by Hopf, at Wùrz- burg, in 1828. The word is so barbarous and senseless that it is not wonderful that no one should be proud of it. CASES OF HJEMOPHILIA. by the American physicians^ who first described cases Chap. I. of this disease. In Franca the disease is now always called hémophilie. In the older books it is called dia- these hémorrhagique, hémorrhaghie constitutionnelle, pur- pura constitutionneL The patients are called hommes saignants, but more commonly the German Bluter is used. The notes of a few cases of haemophilia which bave fallen recently under my own observation are bere given : the first four cases bave been already published.* Ali the patients were natives of London. Richard Bickell, born Aprii 28, 1859, was brought to Saint Bartholomew's Hospital on Aprii 27, 1871. The following bistory was given by bis maternal grandmother. His father is alive, aged 35 ; by occupation a paper- hanger ; he was born in Devonshire. He is not sub- ject to bleedings, nor are any of his brotbers or other relations, to the best of informant's knowledge ; they do not suffer from gout. This man enjoys good health, but is very subject to catarrhs. He was no relation to his wife. His mother had always weak health ; she was not subject to excessive floodings or menstruation. She died when 29 years old. She had been delivered of ber fourth child about a month, and was sitting in an easy ^ Otto, Medicai Reposùoty, New ^ In the Saint Bartholomew* s York, 1803, voi. vi. p. 3. Hospital Eeports, 187 1, voi, vii, p, Hay, New England Journal 0/2^, Medicine and Surgery^ Boston, 1 8 1 3, voj. ji. p. 223. CASES OF HJEMOPHILIA. Chap. I. chair, apparently very well, in the same room with in- formant, when she suddenly called out : Mother, it is dark ; she fell back, and was dead in a few minutes : during ali her life she had had a beating at the heart, and the last few years she was subject to a cough in the winter. She was an only child ; she married when 20 years of age, and had four children : Richard, the present patient, a bleeder. Girl, aged io, not a bleeder ; she enjoys good health. Girl, aged 8, not a bleeder ; she enjoys good health, but this summer has been subject to bleedings from the nose. Boy, aged 6 ; he bleeds often at the nose ; and when the bleeding comes on it lasts three or four days. When he is bruised, there are seen large black and blue patches under his skin ; but no spontaneous ecchymoses bave been noticed. He was vaccinated when he was three months old, and the bleeding was not more than is usuai with other children. The vesicle ran its usuai course. AH these children were born in London. My informant says that she knows none of her own relations to be subject to bleedings. Her husband is subject to a cough and symptoms of dyspepsia, but not to bleedings or gout. ^ She herself is 55 years old, very stout. AH her life she has been subject to * gravel in the kidneys,' and says she has passed several small stones with the urine. The patient was born at the full time ; there was no difficulty in stopping the bleeding after the cutting of the navel string, nor any bleeding when the stump fell off. The boy was vaccinated when three months old, there was no unusual bleeding, the inoculation being CASES OF HJEMOPHILIA. successful. The mother suckled him herself for twelve Chap. I. months. When the teeth of the first dentition carne through, there was no unusual bleeding. But these teeth de- cayed early ; and when he was between 4 and 5 years old, one of the back teeth was taken out for this reason. The bleeding fifoni the socket lasted three weeks, and defied every styptic. An attempt was made to use the hot iron, but was abandoned from the restlessness of the child. The boy was quite bloodless when the bleeding carne to an end of itself. This was the first haemorrhage of any kind noticed. When he was 6 years old, bis left knee began to swell, and this joint has been swoUen, off and on, ever since. The knee may keep well for three or four months ; it then begins to swell, and will be painful and large for several months at a time, so that the boy is seldom free from trouble with bis joints. Sometimes, as the swell- ing is disappearing in the left knee, it appears in the right, and vice versa. Sometimes the ankles swell ; but the left knee is the joint most commonly disabled. No swelling has been noticed in any other joints. No difference has been noticed in summer or winter, or in cold or wet weather. He was 3 years old when he had the measles ; and was 5 years old when he had the whooping-cough, after which he was six weeks in the Hospital for Sick Child- ren. He has never had scarlet fever, small-pox, or any other disorder. Three months ago a tooth gradually became loose, and though great care was taken that it should not be puUed out, yet one night, when it was attached by a CASES OF H^MOPHILIA, Chap. I. mere thread to the gum, it carne away ; the bleeding then lasted a week, defying such styptics as alum and gallic acid ; after ceasing for a few hours, it began again, and lasted another week, making a fortnight al- together. He has never been subject to epistaxis or haematuria, nor to any other spontaneous haemorrhages, When blisters are applied, as, for example, to the knee, no ili effects foUow. The boy's schoolmaster tells my informant that he is * first class at bis hook.' The boy himself says he is glad to go to school, and ' he seems intelligent for bis age. The boy has brown hair, blue eyes, and a thin skin. The cheeks and eyes are sunken, he looks thin and pale, and has a worn aspect, such as those bave who bave suffered much pain. The chief trouble is bis knee : two nights ago it was swoUen as big as bis head ; but the next morning it had very greatly diminished. There is now a swelling which fluctuates very plainly, and upon which the patella floats. The right ankle is also swoUen, but not very greatly: neither joint is pain- fui. There is nothing unnatural about the heart. The knee was strapped ; and the grandmother was told to give bim a teaspoonful of cod liver oil and steel wine three times a day. May II. — The boy has remained under observation until the present time. He is now shedding bis back milk teeth, and there is a Constant oozing of blood going on from the gums. James Cameron, aged 24, first came under my notice in October 18O8. He was born in Clerkenwell, and was CASES OF HJEMOPHILIA. 2l sailor by occupation, going in steam and sailing ships Chap. I. to Australia, Constantinople, &c. He was a man of middle stature, fair hair, and light gray eyes. There was a complete absence of whiskers and only a slight moustache ; but abundance of hair over the pubes. The skin was thin. The intelligence was somewhat below the average. He was suffering from erysipelas of the head and face ; and in consequence of this a col- lection of matter formed under the skin of the neck, just below the parotid gland. On October 17, the abscess was opened by a small incision, which bled, at the most, but a few drops ; pus escaped, and the neck was poulticed. On the igth a sihus had formed which admitted a probe for two inches ; the skin was then cut through on to the point of the probe, and a few threads passed through the sinus to assist the drainage : some slight venous haemorrhage foUowed. He went on well till October 23, when the bottom of the sinus began to bleed: iced water and plugging were of no avail ; indeed, the plug- ging caused such a sensation of choking that the lint had to be taken out. On October 25, the skin over the sinus having sloughed, it was divided, and ali the coagula turned out. Thereupon the bleeding ceased. On October 28 there was again slight bleeding, and on October 30 the wound was granulating. He now stated that he had been subject ali bis life to bleedings upon slight accidents ; that he had often been in hospital for the bleedings from small wounds, diffi- cult to stop ; and that, if he had a tooth drawn, the bleeding lasted for days. He had never suffered from s^V^llings of the joints. The mother of the patient gave me the following 8 CASES OF HJEMOPHILIA, Chap. I. story. She herself, aged 64, enjoyed good health, and was not a bleeder, but ber father was, and he was tbe first bleeder in ber family of wbom sbe knows. Tbis man married a wife to wbom be was no rela- tion, and bad by ber a numerous family of sons and daughters, onlytwo ofwbom reacbed maturity. My in- formant did not know tbe causes of tbe deatbs of ber brothers and sisters, or wbetber tbey were bleeders. Of the two children wbo grew up one wasmyinformant, and the other, a man, not a bleeder, died aged 64, of * cancer of the tongue.' He bad no children. My informant was twice married : in neither case was her husband any relation. In ali sbe bad twelve children : By first marriage : 1. Boy, not a bleeder, died, aged 40, of poison. 2. Boy, not a bleeder, died, aged 5, of small-pox. By second marriage : 1. Boy, alive, age not exactly known, but over 35, is not a bleeder. 2. Boy, died, aged 3, of wbooping cougb, not a bleeder. 3. Boy, alive, aged 32, not a bleeder. 4. Boy, died, aged 6, of * typbus fever,' not a bleeder. 5. Boy, alive, aged 29, a bleeder. Tbis was first noticed wben be was eighteen montbs old ; be bad a fall, bit bis tongue, and bled furiously. The motber says be is a * frightful bleeder ;' if he has a tooth loose or a cut made, he bleeds * awfully.' 6. Boy, died, aged 25, of dropsy and diseased heart foUowing rbeumatic fever. He was a bleeder. Tbe motber believes he used to bave the gout, for he bad CASES OF HjEMOPHILIA. 9 * chalk stones up the sides of his feet.' Hard masses Chap. I. could be felt under the skin, but they did not come through. He was six years old when he had the rheu- matic fever, and was seven years of age when the diseased heart was first recognised. 7. Boy, died when three or four years old of scarlet fever ; a bleeder. 8. Miscarried at six months of a male foetus. ^ 9. Is patient, aged 24. He was first noticed to be a bleeder when he began to shed his milk teeth at six years old. 10. Girl, died at four years of age of * typhus fever ;' not a bleeder. The patient's father is 68 years old ; he enjoys good health, and is not a bleeder, nor are any of the paternal relations ; but both the father and his relations are gouty. The father had only one brother who died gouty ; and who had only two children, both of whom died idiots in lunatic asylums, My informant has only one grandchild, aged g months ; no signs of bleeding bave appeared (October, 1868.) Cameron was alive and well in Aprii 1871 ; but his mother died in the autumn of 1869, James Day, aged 8 yeàrs, was brought by his mother to Saint Bartholomew's Hospital on Aprii io, 187 1, suffering from repeated tleedings from his mouth. His mother gave the foUowing account of his family. The father is alive, aged 30 ; he was born in White- cbapel, and enjoys good health. By occupation he is (. r' 1l^ 9 , t k IO CASES OF HJEMOPHILIA. Chap. I. a portar ; he is not subject to bleedings nor to the gout. He has had two brothers, both older than himself ; one aged 40, is subject to bleedings ; when he has a tooth drawn, or wounds himself, a bleeding foUows which is difficult to stop. This man has seven children, three boys and four girls, who are not subject to bleedings. The other brother was also subject to excessive bleed- ings upon slight causes ; he was killed, age unknown, while following bis trade as an armoury sergeant, by the explosion of some weapon. The father had only one sister, who died, aged 30, of consumption. She had only two children, both girls ; they are not subject to bleedings. The mother, aged 30, looks in good health ; her menstruation has always been regular and not exces- sive. She has only once been pregnant. She has two brothers, but they do not suffer from bleedings ; none of her relations are subject to bleedings to her knowledge. She is no relation to her husband. The boy was born in Bethnal Green, at full time ; the mother does not remember any difficulty with re- gard to the falling off of the navel string ; he was suck- led till fifteen months old. When sixteen months old he was vaccinated, and the incisions were unattended by any unusual bleeding, and the vesicles ran their usuai course. When two years old he had the measles, and the mother thinks he has never been well since. He has had no other disease of childhood, as whoop- ing-cough, scarlet fever, or small-pox. He has lived in London ali bis life. The mother has never noticed any black or blue spots on the skin ; nor when he is bruised do the parts be- CASES OE HJEMOPHILIA. 1 1 come much ecchymosed. He is not subject to pains in Chap. I. the limbs or swellings of the joints. The tendency to bleeding was first noticed when the boy was five years old ; it then showed itself by repeat- ed attacks of epistaxis which lasted for a quarter of an hour or more; these were always more severe in the summer than in the winter, and then came on as well by day as by night. The bleeding occurred several times in a week. But for the last four months the bleeding from the nose has ceased, and the bleeding now Comes from the mouth, but she has not noticed from what part. This bleeding only comes on at night ; yet the mother says it happens every night. The boy has no unusual bleeding when a tooth is taken out or when he cuts bis finger. He has very light coarse hair and gray eyes ; the skin is perhaps a little delicate, but the veins are not prominent. Nothing unnatural can be seen in the mouth ; the first sound of the heart at the base is not healthy. The mother complains that he reads two much, and boy is certainly more intelligent than those of bis class and age are wont to be. He is thin, but bis appetite is good. He is chilly, and complains much of the cold. He was told to take a teaspoonful of cod liver oil and steel wine three times a day. The patient stili remains under observation (October, 1871) ; the general health greatly improved, and the bleedings bave disappeared for two months. The tinc- ture of the perchloride of iron in io minim doses seems to bave had the best result as an astringent. Janaes Hick§, born Aprii 28, 185 1, applied at Saint 12 CASES OF HjEMOPHILIA, Chap. I. Bartholomew's Hospital on Aprii 26, 187 1, for the relief of bleeding from the nose. He said that his father was alive, 45 years old, that he enjoyed good health, with the exception of frequent bleedings from the nose, which, however, are now easily stopped ; when a young man he us^d to bleed 'just as I do,' after wounding himself, but a wound is not now followed by any extraordinary haemorrhage. The patient has never heard of any of his father's re- lations being subject to bleedings, or to the gout, his father is not subject to the gout, nor is he any relation to his wife. The mother is alive, aged 47 ; she enjoys good health, and is not subject to bleedings. The' mother's bro- thers are not subject to bleedings. From this marriage there were seven children : 1. Present patient. 2. Boy, aged 18. He bleeds often from the nose, and the bleeding is difficult to stop when he is wounded. 3. Girl, died aged 18 months, of measles. 4. Boy, alive, aged 14. He has pretty good health, but the. bleeding is considerable when he is wounded. 5. Boy, alive, aged 12. When wounded he bleeds much less than the others. 6. Boy, alive, aged 8. Now he has very good health ; but he *has been out of his mind, caused by a fright.* He bleeds very slightly when wounded. 7. Boy, died, aged 12 months, of * fever.* This patient was born in Bermondsey, and has lived in London ali his life. He is a lighterman on the Thames. He says he has been subject to bleedings from the nose since his birth. He also says that he bruises very CASES OF HJEMOPHILIA. 13 readily ; and that when he is wounded he bleeds so Chap. I. much that it is only stopped with great difficulty. Latterly, however, he has taken to putting tobacco on the wound, and he says that this stops the bleeding in five minutes. He points to a cut on the pulp of the finger, which was done five days ago, and which is now quite healed. He has never had a tooth drawn. He has never noticed any petechiae, and has never passed blood in bis water ; occasionally there is a little blood in bis spit, which he thinks comes from the gums. He is not subject to swellings of bis joints ; but he has great pains in the right knee, which are worse at night. Sometimes these pains are so great that he walks lame. This man has light brown hair and gray eyes : he has no whiskers, but a slight moustache. There is a good deal of hair about the pubes. The skin is thick ; the man's intelligence considerably below the average. The hands and feet are cold, and he says he feels the cold much. The bleedings from the nose bave much increased during the past fortnight ; they come on most at night, and in the early morning, and he has several times been obliged to plug the anterior nares with cot- ton. Great improvement in the general health and con- siderable respite from the bleedings were obtained ; twenty minims of the tincture of perchloride of iron were given three times a day with cod liver oil. In a month the bleeding from the nose had almost dis- appeared, while the pains in the keee were greatly di- minished. He ceased shortly after to attend at the Hospital. 14 CASES OF HjEMOPHILIA. Chap. I. William Robins, aged 23, applied at Saint Bartholo- mew's Hospital on August 26, 1871, for the relief of swelling of the knee. His father is alive, aged 47, subject to * rheumatic gout' in ali his joints for about 20 years ; he has chalk- stones in his hands ; and ali his family are subject to the gout. He is not subject to bleedings ; and he is no relation to his wife. Mother alive, aged 40. She enjoys excellent health and is not subject to bleedings. She had only one brother, who was subject to bleedings from slight causes from his birth. When he was 20 years old, he met with some accident and broke his leg : it was cut off in one of the London Hospitals, the bleeding could not be stopped, and he died. The patient's mother has borne six children : 1. Boy ; present patient. 2. Boy, aged 21. He is not subject to bleedings, but enjoys excellent health. 3. Boy, died aged 7. He was subject to bleedings, 4. Boy, died a baby. 5. Girl, died aged 4. Cause unknown, 6. Girl, alive, aged 5. In good health. The patient is a painter by trade ; he is unmarried. There is a slight blue line round his gums. He says he has been subject to bleeding since he can remember ; his mother tells him that she first noticed this disposition when he was about 2 years old, from frequently-returning bleedings at the nose. When a child he used to bleed abundantly when he was pricked or scratched. The last timethat he had any serious bleeding was about 3 years ago from a cut on the palmar surface CASJSS OF HJEMOP BILIA. 15 of the rootofthe left forefinger; thescar isless than half Chap. I. an inchlong, and he says the wound was very slight; yet he was treated at Saint Bartholomew's for three weeks before the bleeding could be stopped. When he is struck, a large black and blue mark is nearly always left. Occasionally he notices similar black and blue spots on his arms and legs, without remembering a bruise or blow preceding them. When the patient was about 4 years old, his mother first noticed a swelling of the right knee ; this swelled, off and on, till the boy was 13 years old, and since that time it has never been of its naturai shape and he has always walked lame. He has sometimes swellings of the ankles, but they only last a week at the most ; once the joint between the proximal and middle phalanges of the right ring finger was swoUen, but no other joints bave been enlarged ; he but occasionally feels pains in the hip and ankle. The knee joint is always worse in winter and upon changes of weather. With the exception of the knee joint, he says that he enjoys pretty good health. Of the spontaneous haemorrhages, epistaxis is his most frequent trouble : it is worse in the summer, and the nose may then bleed as often as two or three times in the day. But this summer the bleedings from the riose bave been much less. His gums sometimes bleed, but he has never brought up any blood or passed blood by stool. He has only once had haematuria : this was last summer. The man is of middle stature, muddycomplexion, and dark brown hair ; he has a good moustache and abun- dance of whiskers. The right knee joint is greatly crippled in its movements, it is also much enlarged on i6 CASES OF HjEMOPHILIA, • Chap. I. the inner aspect and the swelling is very hard, as if the ends of the bones forming the joint were enlarged. The joint itself also seems to contain fluid. His knee joint was strapped and he was given half a fluid drachm of the tincture of the perchloride of iron 3 times a day in water. Sept. 2. He carne back saying that he felt himself much better, both in health and as to the knee joint. Nov. I. 1871. The man has had no bleedings since he has been under treatment. The knee is not de- creased in size. 4 CHAPTER IL HlSTORY OF HiEMOPHILIA. The history of a disease which has only recently be- Chap. IL come known must necessarily be short. There appears to be no notice of haemophilia in the Greek or Latin authors. The earliest account of what seems like this disease is met with in the writings of Albucasis, an Arabie author who lived at Cordova in the iith or I2th Christian century.^ He relates that in a certain village there were men who when wounded, or phlebotomised, suffered an uncontroUable haemorrhage, which ended only with the death of the patient. The same accident happened to the boys of the village if their gums were harshly rubbed; and haemorrhage was the common cause of death amongst them.* I The name in full is Abul- published at Aug-sburg- in 1519: casem Khalaf Ebn-Abbas Al- its title is lÀher TheoricoR necnon Zaharavi ; so that Albucasis Practtcoe Alsaharavii; the passage and Alzaharavius are one and occurs in Tractatus xxxi, Sectio the same person : a fact known ii, Capitulum xv, Folio cxlv. to Schenck, who, in the Elenchus " De Passione fluxus sangui- Auctorum at the beg"inning nis a quocumque locorum. of his Ohservationes Medicee, says " Vidi in quibusdam reg"ìoni- "Alzaharavius, qui est Albuca- bus casale quoddam dictum sis." In more modem times alkiria viros qui narraverunt this was rediscovered by Freind mihi quoniam cum accidit in {History of Physick, London, 4th in corporibus ipsorum aliquod edition, 1750, Part IL p. 126). vulnus mag'num indesinenter * I am obliged to quote from sanguis fluit ex vulnere quous- a barbarous Latin translation que moritur : et recitaverunt D i8 HISTORY OF H^MOPHILIA. Chap. il It has been a good deal doubted if this be a descrip- tion of haemophilia ; but I think the probabilities are in its favour. The tendency to traumatic haemorrhages, one of the most distinguishing notes of haemophilia, is well marked : the tendency to haemorrhage also exists in childhood and adult age ; and it seems likely that it was hereditary, since it occurs amongst many inhabi- tants of a small village. No other disease but haemo- philia corresponds to these characters. Passing by the very uncertain case of Alexander Benedictus,^ published in 1539, we are indebted for mihi super hoc quod quibus- dam ex pueris suis cum fricaret manu gingivas cepit sangiiis fluere ex illis donec mortuus est, Alius vero flebotomatus a minu- tore sanguinis non cessavit ex eo emanare, donec periit, Et universaliter eorum mors ut in pluribus contigit in hunc modum, Haec est res quam nunquam et nusquam vidi nisi in casali prae- dicto, nec reperii hoc accidens ab aliquo antiquorum memoran- tium, nec scio ejus causam, et quod mihi videtur de curatione ejus est quod ille cui hoc acci- dit celeriter cauterizet locum, donec sanguis restringatur, et ego minime probavi hoc, et est apud me monstrum." Alkìria is an Arabie word having precisely the same mean- ing as casale^ a small village or homestead, from the Low Latin casa, (See Ducange's Glossar- lum) . This translation of Albucasis is by Sigismund Grimm : Haller calls it " versio pessima" in which severe condemnation every read- er of the extract given above will agree. There is an Arabie MS. of the Al- Tasrif in the Bodleian at Oxford, but I regret that I have been unable to obtain a translation of this passage from the Arabie, for much light would have been thereby thrown upon the ques- tion whether Albucasis realiy refers to haemophilia. ^ Alexander Benedictus, O/w- nium a vertice ad calcem morbo- rum signa, causcB, indtcaiiones, etc.^ Basileae, 1539, Lib. iiii. Cap. iiii. p. 203. **De sanguinis profluvio e naribus. k. HISTORY OF H^MOPHILIA. 19 our knowledge of the next notice of haemophilia to the Chap. IL learning of Professor Virchow,^ who first drew attention to a passage in the writings of Philip Hòchstetter,^ a physician practising at Augsburg in the beginning of the seventeeilth century. In this he speaks of a boy who shortly after his birth suffered a considerable haemorrhage from the navel ; later on in life he had repeated epistaxis, once at least bloody stools, and spontaneous ecchymoses. This is the best described of the older cases ; few will be disposed to doubt its connexion with haemophilia. " Venetiis tonsor qui- dem cum in naribus pilos incom- modos forcipe concideret, venu- lam incaute secuit, tantoque impetu sang^is erupit, ut sis- tendi modum medici plurimi non adinvenirent, et ille misere vi- tam finivit." ^ Virchow, Archiv ^f, path, Anat. Bd. xxviii. p. 426. 2 Philippi Hoechstetteri, Au- g-ustani, Physici Patriae, Rar- arum Observationum MedicinoLium Decades Sex, Francofurti et Lip- siae, 1674, Tom. I. Decas ii. Casus Nonus, p. 1 70. "Nati modo sanguinem fundens largius umbilicus et adulti ad hae- morrhag-iam pronae nares cum suggillatione. '^Puer quidam sanguinem oh non rite ligatum umbilicum re- cens natus copiosum fudit : mater remotis fasciis infantem comma- Qulatum videns, perterrita in feb- rem et phrenesin incidens vitam morti cessit; puer non deterius habens; h^morrliagise narium dum adolescit- maxime fit ob- noxius ; setatis nono copiosa fuit, ut adstantibus terrori esset. Ideo- que adhibitis refrigerantibus et sanguinem sistentibus medicinis, narium stilla desiit, at feces cum sanguine fluenti et concreto pro- diere, mixta, suggillataque, seu maculae sanguineae rubrae, post cseruleae per cutim passim effloru- ere, in facie, pectore, dorso, artubus, quae tandem flavae factae disparuere. Sequentibus annis, cum similis h^morrhagia ac suggillatio adesssent, seque- batur scabies ; quae dum curatur mundantibus sanguinem et pur- gantibus corpus, promovetur haemorrhagia. Quare undeci- me anno aetatis venam adperui commode, teneram haud metu- ens aetatem/* 20 mSTORF OF H^MOPHILIA. Chap. II. There is another case belonging to the seventeenth century, which has been frequently quoted, but which has never before been traced to its originai source. It is the case which is called by the Germans Lowthorp's, or Coxe's. It belongs, however, neither to the one nor to the other, but it is taken from the earlier volumes of the Philosophical Transactions . In a letter from a clergyman in Shropshire the illness and death of a little girl aged about 3 months is described. She was taken with a bleeding at the nose, and ears, and hinder part of the head, for three days. On the third day, the blood carne more violently from the head : she bled also on the shoulders, waist, toes, bend of the arms, at the joints of the fingers and the fingers' ends. She died on the sixth day after the bleeding began. After the child was dead, there appeared in the places, where the blood issued, small holes like the pricks of a needle.' This case was copied into Lowthorp's Abridgement of the Philosophical Transactions. Coxe, the Editor of the Philadelphia Medicai Museum^ commenting upon Smith's case, shortly to be referred to, quotes this case, with * Philosophical Transactions, voi. ix, 1674, No. 109, p. 193. Dee. 14. " Relation sent November 16. 1674. From a very credible and ingenious Person, Mr. Samuel du Gard, Rector of Forton in Shropshire to Dr. Ra. Bathurst Vice-Chancellor of the Univer- sity of Oxford, and by him com- municated to a Friend of his in London." The child died at Lilleshal in Shropshire about Candlemas, 1674: du Gard does not seem to have seen the child either alive or dead, and he says "this Accompt I had from the Mother of the Child, who is a very sober Woman ; and she told it me with tears." He, however, saw some of the clothing stained with blood. 4 HISTORY OF H^EMOPHILIA. 21 others, from Lowthorp's Abridgement. It does not Chap. IL seem to be one of haemophilia ; and the other two cases, quoted by Coxe, of Clopton Havers,' and Ash,* certainly are not. There are two other cases in the same publication which bave not yet, so far as I know, been referred to with respect to haemophilia ; they are deserving ' of some attention. One is a case^ recorded by Dr. Wil- liam Musgrave, F.R.S. ; a Mr. H., formerly a servant to the Queen Dowager, had from bis infancy to the 24th year of bis age, a periodical baemorrbage in one of bis thumbs. The time of the eruption was about the full of the moon ; the orifice was on the right side of the nail of the left tbumb. At the age of 24 he seared this part with a hot iron : it stoppe^ the bleeding for twenty years ; but within a quarter of a year after it he fell into a spitting of blood, bringing up from his lungs vast quantities thereof. Thereafter he fell into a violent cholic, and with this he was ever after often troubled, as also with a spitting of blood. The case, though curious, hardly belongs to haemo- ^ Pht'i. Trans, voi. xviii, 169I, No. 208, p. 51. In a letter to Clopton Havers, the case of a woman is de- scribed who about 3 months be- fore her death began to bleed at the gianduia lacrymalis : she bled till she died. ^ PM. Trans, voi. xv, 1685, No. 171, p. 989. History of a man who began to bleed when 43 years old from the end of his fore finger; this bleeding returned about every three weeks. 3 Musgrave, Pht'l. Trans, voi. xxii, 1701, No. 272, p. 864. The case is quoted by Lefebvre with reference to the phaenomena of Stigmatisation (Louise Lateau de Pois (THainey Louvain, 1870, p. 116). 22 HISTORY OF HjEMOPHILIA. Chap. il philia. There would be no doubt as to the case which follows, did there exist any account of haemorrhages before the 24th year of the patient's life : but unfortu- nately there is no mention of the state of the man's health before this time. As the earlier volumes of the Philosophical Transactions are somewhat difficult of ac- cess, I give the whole of the description, thinking that it may interest some. ** In the Month of January 1729. Daniel Goddardy 2l Gardener, about the Age of Twenty-four Years, at Wisbech in the Isle of Ely^ Cambridgeshire^ happened of a slight Puncture from a rusty Nail in the Sole of his Right Foot. And, notwithstanding there was net wounded any Tendon, or Blood-Vessel, larger than small Branches of Veins, the whole Foot was imme- diately swelled to a very unusual Degree, without any Fever, or other apparent Cause for it. It was also at- tended with great Pain, and an extraordinary Pulsation upon the Part, as in the Wounds of Arteries ; and so dis- tended asif the Blood would burst out of its Vessels. ** Accordingly, after Two Days, upon opening a su- perficial Sinus, to inlarge the Wound, there rushed out immediately such an obstinate Flux of Blood, as would not yield to any styptic Means, longer than the Ban- dage was holden on by some strong Hand. And, although, by this Incision, no Vessels were wounded, but Capillary Veins ; yet this Hcemorrhage continued to shew itself as violent as at first, for Six Days succes- sively, whenever the necessary Means were relaxed. Upon which, for the sake of Revulsione the Patient had a Vein opened on the Arm of the opposite Side ; and it had such a sudden and surprizing Eifect, that k HISTORY OF HJEMOPHILIA. 23 the Flux of Blood in the Foot instantly ceased, and the Chap. II. Wound healed very soon without any further Trouble ; but the Flux of Blood, consequent upon Venesection, became equally as difficult to restrain, as that in the Foot, for the Space of Four Days ; ali which time it would bave continued to flow most violently without the strictest Bandage, as the same Care of the Hand, as before. Perhaps the Period of this Hcemorrhage might bave been much longer, if I had not suf- fered the Ligature on the Arm to be loosened now-and- then, as I judged the Redundancy of Blood required, for the sake of some Evacuation, at each time. After the Bleeding, he soon recovered bis Strength so as to do bis Business in the Gardens ; and continued very well till the Month of March 1730. About the middle of this month, he complained of Sleepiness, and a par- ticular Heaviness ali over bis Body; which was foUowed, in Three Days time, by a violent Hcemorrhage from the Nose. This Flux, in spite of ali Means being tried, ex- cept Venesection, continued Seven Days, and could never be totally stopped, ali this time, for one Hour together. He recovered again in a very short time, and was able to work in the Summer-season, without any Complaints, till October foUowing. Then the Hcemorrhage returned again at the Nose^ as before, with ali the same Circum- stances, and in Defìance of ali Endeavours, continued the Period of Seven Days. Thus it returned in like manner of Bleeding, by Stools, in the Middle of March 1731, and continued to discharge this Way great Quan- tities of Blood, in one Motion, and sometimes two Mo- tions every Day for Seven Days together, in Opposition to the most efficacious Restringents. Also it made its 1 24 HISTORY OF HjEMOPHILIA. Chap. il regular Return by vast Profusions of Blood from the IntestineSy in the Beginning of October following, to the End of the first Period of Seven Days, without Grip- ings, or any such uneasy Sensations. Thus, again, it kept as orderly Returns about the Vernai and Autumn- al Equinoxes of the Years 1732, 1733, with vast Profu- §ion of Blood by Stool, for the usuai Term of Seven Days, agreeing in ali Circumstances with the preceding Years. Likewise at, or very near these two grand Seasons, in the years 1734, 1735, this habitual Hcemor- rhage broke away by the Kidneys and urinary Passage ; and stili constantly, for these Two Years, kept its old 3tated time of Seven Days, without any other Varia- tion. **This young Man was seized in Dee. 1735, with the Small'poXy of the Distinct Kind, which prò- duced such a Change in bis Constitution, that he escaped those periodical HcBtnorrhages, or any other spontaneous Evacuations equivalent thereto, for the Two Seasons of the Year 1736 ; and remained in very good Health till Christmas following, being above Thir- teen Months free from any Symptoms of bis old Erup- tion, But, upon December the 27th, without any pre- vious Notice of Heaviness and Sleepiness, the HcBmor- rhage returned by the urinary Passages ; but much more favourably, and continued only Three Days, Again, on May the I3th following, 1737, he then felt the pre- vious Warnings, and bled again by Urine to the 20th of the same Month ; with this Difference, that for Three Days the Urine was only Coffee-coloured, but after- wards, for Four Days longer, every Discharge re- sembled an Effusion of Blood from a Vein just openecj. HI STORY OF H^MOPHILIA. 25 He presently recovered his Strength, even although the Chap. IL Air was exceeding warm at this Time ; and I saw him Five Months after, very robust and healthy, and, as he told me himself, was free from ali kinds of Tendency to- wards his old Complaint. But he had always the Ap- pearance of too much Fulness, though I am of opinion, that his Constitution did not suffer so much as might reasonably he imagined, from such prodigious Hcemor- rhages. Of my own Knowledge, he had no Return of his Bleeding, or any thing like it, the ensuing Autumn ; but remained perfectly well ali the foUowing Winter Season. Afterwards I had no Opportunity of making further personal Inquiries, but was informed by an in- telligent Man, that in March 1738, this unfortunate Person got a slight Wound again, somewhere upon one of his Legs, which proved equally as difficult, with re- spect to the Flux of Blood, as the first Puncture in his Foot. And, whether from a too strict a Restraint of the HcBmorrhagCj or for want of Venesection, he fell into very violent Convulsions for Four or Five Days, and died in a manner like Suifocation, from too much Redundancy of Blood. ** As this Hcemorrhage never once depended upon any other Distemper, or observed any regular Concurrence with the Revolutions of the Moon, it appears to be a very extraordinary simple Plethora. During the Four Years that this Flux of Blood came from the Nose and Intestines, the Urine was never of a higher Colour than Amber ; nor was there any Symptom of a Fever by the Pulse, or otherways, for the whole Term of the Dis- prder."' ^ Banyer, Phil, Trans, voi. xlii., 1743, No. 471, p, 268, E i6 HISTORT OF H2EMOPHILIA. Chap, il There is also a possible case of haemophilia recorded by Macquart, of a young soldier, who had been subject to repeated epistaxis from bis earliest ìnfancy, and who, during convalescence from pneumonia, suifered a severe attack of haematuria.^ The next notice of the disease is by SirW. Fordyce, who describes a family in Northamptonshire, the father, a daughter, and sons who suffered from repeated haemor- rhages : it is thought doubtful by some if the case of the drummer boy also described in the same place belong to haemophilia.* Ten years after Fordyce's publication there appeared in Germany two notices of the disease neither of which I bave been able to see. One is by a writer in the Medicinische Ephemeridenj p. 267, published at Chemnitz in 1793 ; the other is by Rave,^ published in 1798. This latter is considered by Grandidier, from whom I borrow the reference, to be a disease inter- mediate between haemophilia and scurvy. Next follow a series of observations at the beginning of the present century by the North American phy- sicians. Otto, in 1803, described a family in New England in which haemophilia had existed for 70 or 80 years :* and in 1813, a branch of the same family was described by Hay.^ In 1805, there was published a ' Macquart, Richcird de Hau- neiwissmschafty 2. Theil, 1798, p. tesierck's Recidi d^ observations de 12. Médecine des Hopitaux militcdreSy * Otto, Medicai Repositoty, New Paris, 1772, t. ii. p. 293. York, 1803, voi. vi. p. i. * Fordyce, Fragmenta Chirurgo ^ Hay, New England Journal of tea et Medica, Lond. 1784, p. 41. Medicine and Surgery, Boston^ 3 Rave, Beobachtungen und 18 13, voi. ii. p. 221. &hlUsse am der praktischm ArZ" ^ HISTORY OF HJEMOPHILIA. 27 letter by E. H. Smith, written at New York, Aprii gth, Chap. II, 1794 : in this there is described the case of a little boy ' who used to bleed considerably a few days before bis birthday ; and which bleeding always stopped upon his birthday. He died of haemorrhage 5 days before he was four years old.' Unless a case described in the Esprit des Journaux for January, 1805,^ be one of heemophilia, the next European notices of the disease are by the Editor of Sammlung auserlesener Abhandlungen^ in 1805, and by Consbruch* in 1810, foUowed by careful clinical and posUmortem observations by Blagden^ in 181 7 and James Wilson® in 1819. The next publication marks the transition from the records of isolated cases to an attempt at the scientifìc description of the disease. In 1820, Nasse published his paper Von einer erblichen Neigung zu t'ódtlichen Blut^ ungen/ in which.most of the published cases are coUect- ed, and a general view is given of the disease. Schòn- lein's influence at this time began to be felt. He prò- posed a name for the disease and introduced it into systematic Pathology. Under his teaching, many in- augurai dissertations on heemophilia were published at * E. H. Smith, Philadelphia ned, Bd. xxx. Stùck v, p. 1 16. Medicai Museum, voi. i. p. 284. 5 Blag-den, Med.-Chir. Trans^ * This pubHcatìon, I regret, I VpL viii, p. 2:^^, bave been unable to 3ee, ^ James Wilson, Ledures on th^ 3 Sammlung auserlesener Ahhand- Blood, &c. Lond. 18 19, p. 4 IO. lungeny 1805, Leipzig, Bd. xxii. 7 Nasse, Horn's Archiv, J820, Stùck ii. p. 275. Mai-Juni, p, 385, 4 Consbruch, Jlufeland's Jouf'^ 28 HISTORY OF H2EMOPHILIA. Chap. II. Wiirzburg and Berlin. In 1829, Rieken' published his monograph which added greatly to the general know- ledge of the disease, although it contains some opinions which cannot now-a-days be endorsed. After 1820, the history of haemophilia becomes al- most entirely German. The United States, after affording one or two more examples of the disease,* dis- appear almost completely from the literature. Eng- land, indeed, collects a great mass of material of single cases, which no one, however, takes the pains to ar- range or digest. In France, the disease attracts but a fitful attention ; and in the rest of Europe it seems to be unknown or disregarded. But in Germany from 1830 to 1850, not only are a great number of cases coUected, but tolerably com- plete descriptions are met with in the text books of Schònlein, Canstatt, Neumann, Fuchs, &c. Two theories as to the pathology of haemophilia prevailed : one, the favourite doctrine of Schònlein, that the disease was related to cyanosis and malformation of the heart : the other, that it was a form of anomalous gout or * scrofula.' In 1849, Wachsmuth^ published a very good mono- graph on haemophilia, containing many new observations and thoughts : and a year after, Lange's posthumous statistical researches were published in Oppenheim's Zeitschrift ; and, so far as I am able to judge, this work was done with much care and discretion. In 1854, I Rieken, Neue Untersuchungen ^ The brothers Buel, Coates, in Betreff der erhlichen Netgung zu and Hug-hes. todtlichen Blutungetty Frankfurt ^ Wachsmuth, Die Bluterkrank- a.M. 1829. heii, Magdeburg, 1849. HISTORY OF HJEMOPHILIA. 29 Virchow gave a good account of the disease in his Chap. IL Handbuch der speciellen Pathologie und Therapie : and in the foUowing year Grandidier published his treatise, Die Hàmophiliej supplemented by a report in Schmidt's jfahrbiicher for 1863. Of late some important cases have been published : by Lemp' in 1857, containing the account of a post-mortem examination made by Professor Virchow; by Gavoy,* in 1861, containing an account of the microscopical examination of the blood vessels and an analysis of the blood ; and lastly by Otte^ in 1865, containing observations upon the influence of the weather on the occurrence of the bleedings, and a further analysis of the blood. Lemp, De Haemophilta non" ^ Otte, Ueher die Bluterkrahkheit, nulla, Diss. Inaug. Berol., 1857. Leipzig, 1865. ^ Gavoy, LMmophilie^ ou diathèse hémorrhagiqtiey Thèse de Stras- bourg, 1861. CHAPTER HI. ìEtiology of H^mophilia. Chap. III. When the first descriptions of this disease were pub» lished, it was thought that haemophilia occurred amongst the boys only of a family, and that the girls were exempt.' By the graduai collection of cases, however, this as- sumption has not been maintained ; although* women are far less disposed to the disease than men. Lange,* for instance, collected in 1849 ali the published cases, and he found that the numbers were 227 or 229 boys to 31 girls, a proportion of 7 : i. Butin 1855, Grandidier^ found that the numbers had risen to 452 boys and 32 girls, an increase of one case only amongst women ; this is a proportion of 14: i. But in 1863, the same writer* found that the ratio had fallen, and was as 11 : I. I believe that this lowering of the proportion is caused by the admission of cases that bave small claima to be considered haemophilia : indeed in Grandidier's first list there are several cases that must be looked ìipon with great suspicion, such as instances of umbiU Ical haemorrhage in the new born, or uncomplicated menorrhagia in adults, * Otto, Medicai Repositoty, New ische Untersuchungen ùber die York, 1803, voi. vi. p. 3. Bluterkrankheit, p. 157. Nasse, Horn's Archiv, 1820, 3 Grandidier, Die Hàmophilie, Mai-Juni, p. 390. 1855, Leipzig-, p. 87. 2 Lange, Oppenheim's Zeit- 4 Grandidier, Schmidt's Jahr^ ^chrifit 1851, Bd. xlv, Statist- ^«V^^, 1863^ Ed. cxvii, p 335. JETIOLOGY OF HJEMOPHILIA. 31 The women also who are the subjects of haemophilia Chap. III. rarely present typical instances of the disease. The" danger to life is infìnitely less than in the opposite sex. Grandidier, indeed, says that 16 out of the recorded cases have fallen victims to haemorrhage ;^ but from the circumstances mentioned above, these figures must not be received with too implicit a faith. Most of them have died from bleedings from the genital organs, and Wachsmuth has recorded a case, where the rupture of the hymen on the marriage night caused the death of the bride from haemorrhage.* The disease, also, affects women with a lower degree of intensity than men : they do not bleed more than is usuai when wounded, and the disposition may limit itself to the occurrence of spontaneous haemorrhages, or to early, abundant, and prolonged menstruation. Floodings are common both after delivery, and at the time of the cessation of the catamenia. The mother and daughter, mentioned by Nasse,^ belonging to a bleeder family, died of profuse floodings about the cli- macteric. Hereditary disposition is the best ascertained cause of haemophilia. Out of 98 families, there was a disposi- tion to haemorrhage in the parents, grandparents, or cousins, in 52.* Of the remaining 46 families, the parents enjoyed good health in 20, but in 26, they suf- fered from gout, scrofula, whatever the exact meaning of that term may be, syphilis, lung and heart disease. ' Grandidier, loc, di, 3 Nasse, op, «/., p. 426. « Wachsmuth, Die Bluterkrar^- * Grandidier, Schmidt's Jahr- heit, Magdeburg, 1849, p. 9. buclier^ Bd. cxvii, p. 336. 32 ^TIOLOGY OF HjEMOPHILIA. Chap. III. Grandidier is inclined to think that the mothers are more often in bad health than the fathers/ I think that the disease may he traced to hereditary transmission oftener than is allowed. When, for exam- pie, ali the boys, or nearly ali the boys of a family are bleeders, it would seem more likely that there is an hereditary taint rather than a generation de novo of the disease, This, of course, may be rebutted when there exist records of the family for many generations past ; but among the poor, nothing is usually known before the time of the grandparents, and often not so far back as that, It will be seen that the disease may make its appearance at long intervals, remaining latent, if I may use the expression, in the women of the family for two or more generations. When the disease cannot be traced to transmission, but little is known with cer- tainty as to other causes. Some bave carried the idea of hereditary disposition to an extreme, and asserted that ali bleeders bave a common ancestry. But this is plainly impossible,* Others bave thought that the disease arises when intermarriage of near relations is allowed '^ and support seems to be given to this view from the apparent greater prevalence of the disease in Germany where the marriage of cousins is so little 1 Grandidier, loc, cit, 2 The case of Heymann's (Arch,/, path. Anat, Bd. xvi, p, 182) of a Mussulman family in Sumatra would have proved this point conclusively, had the writer stated that there had been no in- fusion of European blood; for the Dutch had onqe a factory iq the island, 3 Rieken, Neue Untersuchtingen in Betreff der erbltchen Neigung zu t'ódtlichen Blutungen, Frankfurt a.M. 1829, p. 102. Heyfelder, Medizin, 2^'tung (Verein's), 1833, p, 246, ^TIOLOGY OF HJEMOPHILIA. 33 discouraged : it is also more common among the Jews, Chap. III. who are obliged to intermariy. Rieken^ has tried to prove some relationship in haemophilia to gout. But, in truth, nothing is known of the circumstances which commonly surround the production, de novoy of this disease. That the disease can be produced in a healthy child by food or external agencies is extremely unlikely. Yet such a case has been brought forward by Guépratte :^ a healthy boy in the island of Guadaloupe was suckled by a black woman, already exhausted by three wet- nursings foUowing dose on each other ; she also fed the child badly with much fruit, and lived in a damp low hut. The boy acquired ali the appearances of haemo- philia, including a swelling of the ankle ; but recovered after a long dietetic treatment. The description of the case to which I bave had access, leaves upon the mind the impression of purpura or some allied disorder, and not of haemophilia. Such a rapid recovery has never yet been seen in this latter disease. A case has been recorded by Mutzenbecher, in which it is supposed that the disease was generated de novo.^ A strong and healthy boy was born of healthy parents, who were quite ignorant of any disposition to excessive bleedings in any of their relations. When the child was 9 months old, and stili being suckled, the mother barely escaped being outraged by some French soldiers in a wood near to her home. Greatly frightened, the woman fainted on reaching her house ; and when she had scarcely recovered her senses, she gave her child * Rieken, op. di, p. 87. 3 Mutzenbecher, quoted by a Guépratte, Canstatt's Jahres- Grandidier, op, cit, p. lOO. berichtfuer 1844, Bd. iii. p. 291. F 34 ^TIOLOGY OF H^MOPHILIA. Chap. IIL the breast. From that moment the child lost its healthy look, and shortly after showed symptoms of haemophilia, ecchymoses and bleedings, traumatic and spontaneous. Two other boys, also bleeders, were also bom of this woman. Even if this be a case of the generation of haemophilia de novOf there is little evidence to show that the mental emotion suffered by the mother was the commencement of the disease. Haemophilia seldom shows itself before the end of the first year ; and it may probably bave been incubating in this child, until some exciting cause brought out symptoms. Again, the woman bore two other children, bleeders : a fact which makes a here- ditary transmission probable ; and wherefore, then, seek for a cause of haemophilia in the ingestion of a small quantity of milk, secreted while the nurse was under the influence of depressing emotion ? a cause which seems quite unequal to the production of so great a result, nothing less than a complete revolution in the constitu- tion of the infant. There is also a case recorded by André, of a woman who during her third pregnancy saw one of her maids bleeding from a wound on the head. She was delivered of a daughter who died, when io weeks old, of a bleed- ing from the scalp and ends of the fingers. Two boys were afterwards begotten, who both died, when io weeks old, of haemorrhage. Here again, children with a disposition to bleed were begotten long after the first men- tal disturbance ; and further, the children did not live long enough to make the diagnosis of haemophilia un- questionable.' ^ André, SchmìdV s /ahrbùcA^r, Bd. Ixxii. p. 142. ^ETIOLOGF OF HJEMOPHILIA. 35 It is well, nevertheless, not to lose sight altogether of Chap. III. the influence of the emotions, specially of the depressing emotions, in the production of haemorrhage. A sud- den great fear is not uncommonly the starting point of a haemorrhagic disposition in women : and the emotions of grief and anger may he foUowed by haemorrhages.^ I beUeve that the emotions bave a far greater influence upon the tissues than is generally thought. The daughters of a bleeder family are to a great ex- tent protected against haemophilia. But though they are themselves so slightly liable to the disease, yet they possess in a very high degree the faculty of trans- mitting haemophilia to their sons. The women may ap- pear perfectly healthy : they may marry perfectly healthy husbands ; and yet bear a family ali the boys of which shall be bleeders. Something like this is not very un- frequently seen in gout, a disease which rarely attacks women. The father and brothers may be gouty : and a daughter, remaining herself free from the disease, may bear a son who shall bave well-marked gouty parox- ysms, no other hereditary taint, and no exciting cause, being apparent. When women, who are themselves the subjectsof hae- mophilia, bear children, their sons appear to be neither more nor less liable to the disease than if their mothers hfld sprung of a bleeder family, but had been them- » Joseph Frank, Praxeos Medi- Mèdectne pratique, Paris, 1838, t. i. eoe Untversae Praecepta, pars ii. p. 57; and Lordat, Trcàtè des Hè- vol. ii. sect. ii. De Amore effraeno, morragies,Vzx\%, 1808, p. 84. The Edit. Sec. Taurin. 1821, p. 255. influence of the soul formed an See also Haller, Elem, Phys, important part of StahPs theory lib. xvii. sect. ii. § 6. et seq, ; of haemorrhages. Gendrin, Traiti philosophiqiu de 36 JETIOLOGY OF H^MOPHILIA. Chap. III. selves free from the disease. Reinert records two cases of this kind, which are, indeed, rare ; in one, the woman bore 6 sons and 2 daughters, of whom only 3 sons were bleeders ; in the other, the woman bore 4 sons and 2 daughters, and only one son was a bleeder.' When the men of a bleeder family, themselves the subjects of haemophilia, beget children, it is not often that they transmit the disease directly to their children. There are several cases on record where the disease has passed from father to son ;* but it is not the rule, and in some of these cases, the father was not sprung of a bleeder family and the account given of him scarcely warrants the assumption that he was the subject of haemophilia. Transmission through the father directly to the son is not uncommonly seen when the father's brothers are bleeders, but he himself has escaped. But although the children of a man, subject to hae- mophilia, do not themselves suffer, yet some of the grandsons, the daughter's sons, are almost sure to be affected ; the sons' sons escape, but the disease re- appears in the grandsons by the daughters, their sisters again transmitting the disease to their sons. Do the grand-daughters by the sons pass the disease on to their offspring ? and do the brothers of bleeders, them- selves free from haemophilia, transmit the disease by their daughters ? There are, unfortunately, no very clear observations on these points. Most of the histo- * Reinert, Ueher Hàmophilie, Bd. xxvii. Heft. ii. p. 378), where Diss. Inaug". Gòttingen, 1869, the disease descended in ajew pp. 4 — 6. family from the father to his son, * Notably the case described and thence to the grandson. by Steinmetz (Rust's Magaztn, JETIOLOGY OF H^MOPHILIA. 37 ries are taken from the families of the artizan class, and Chap. ili. these, as already remarked, are unsuited for any obser- ^~^ vations as to descent. Through how many generations haemophilia may be transmitted is unknown ; and until the disease bave been under continuous observation for a longer time, no sufficient data can be obtained. In the village of Tenna in the Swiss canton of Graubùnden, there are two famiHes of bleeders which bave certainly existed since 1770, and probably for some time before this date. The tradition in the village is that a young man was condemned to death for a petty theft by a judge who was bis godfather ; and that at the supreme moment the thief called down a curse upon the judge, and upon bis children after bim. Be the value of this tradition what it may, it points to a time when the two families were closely allied : and in 1770 they were not related to eacb other.' It tbus seems probable that the disease has lasted for many years before the first written re- cords. Of two of the American families there are accounts which extend through 4 or 5 generations* and Kuester says that the sons in the family of bis patient bad been bleeders as far back as they could remember.^ It seems improbable that the disease, once establisbed in a family, sbould ever die out ; but there is one in- 1 Grandidier, op, di. p. 21. 3 "Ein Curgfast, 28-30 Jahre ^ Hay. New England Journal of alt, erwiederte wie alle Medicine and Surgety, Boston, 1 8 1 3, mànnlichen GÌ leder seiner Familie voi. ii. p. 221. From 17 15 to seit undenklichen Zeiten Bluter 18 IO. wàren" (Kiister, Caspar's Wooken- ìUnghe^, American Jour?udo/Med' schri/i, 1847, P* 282.) ical Science, 1833. voi. xi. p. 542. 38 MTIOLOGY OF HJEMOPHILIA. Chap. ih. stance recorded in which the disease has been reported to be insensibly disappearing.' From a table of 52 families given by Grandidier in which the number of children is stated, it appears that ali the sons were bleeders in 24, that is, in nearly half the families.' In 3, ali the children, sons and daugh- ters, were bleeders ; but in these 3 families there was only one daughter. In 13 out of 54 families, one or more of the daughters, usually, however, only one out of several, were the subjects of haemophilia. As a rule, those members of the family, whether men or women, who are not themselves subject to bleedings, enjoy good health. Wachsmuth^ was the first to notice the uncommon fertility of the women belonging to bleeding families. In 12 families there were no less than 112 children, giving an average of nearly io children for each family, a number far above the usuai proportion. The mor- tality amongst the children is very great, and it is per- haps to compensate for this that so many are bom. Those in the family who are not the subjects of haemo- philia do not seem to be more liable than other children to death at an early age. Lange* found that of 64 such children, 13 were dead at the end of the first year, and X4 at the end of the fifth, a mortality by no means high. It has appeared to me, in looking over the recorded cases of haemophilia, that, where ali the boys are not ' Journal des Progrhy 1828, voi. -♦ Lange, op, cit, p. 165. It is xi. p. 244. not clear whether Lang-e meant * Grandidier, op, di, p. 97. that 14, or 27, out of the 64 were 3 Wachsmuth, op, di, p. 35. dead at the end of the 5th year. JETIOLOGY OF HJEMOPHILIA. 39 the subjects of the disease, the first born are more Chap. III. exempt than the others. In the present state of mat- ters, there are too few cases given in sufficient detail to he capable of being used for statistical purposes : but I venture to draw the attention of observers to this point in order that it may be either disproved or con- firmed. It is a matter open to discussion whether haemophilia be more frequent in one country than another. There can be no doubt, however, as to the country in which the largest number of cases has been described. Germany has recorded nearly 50 per cent, of the known cases ; England, less than 20 per cent, including a few Scotch and Irish cases ; France, the United States of North America, and Switzerland, about io per cent. each. A few cases bave been described by German physicians in the German provinces of Russia. One or two cases bave been reported from the Scandinavian kingdoms. But Spain has afforded no case since the days of Abul- casis.' In Italy, Turkey, and the rest of the civilized world, the disease seems to be unknown, or to be dis- regarded. A few years ago, the history of a bleeder family in Sumatra was published by a German phy- sician :* but this is the only case from Asia that has ever been brought forward. From the large proportion of cases which bave been recorded by German, English, and American writers, it has been thought by some that haemophilia is a special ^ This writer was born and that country, than, as so many died near Cordova, in Spain : authors assert, in Arabia, it seems, therefore, more proba- 2 Heymann, ^rf>4.y./aM. Anai, bla that his case was observed in Bd. xvi. p. 182. 40 MTIOLOGY OF HjEMOPHILIA. Chap. III. inheritance of the Teutonic race. Some light may be thrown upon this hypothesis by a study of the history of the disease. Nasse first published his monograph on haemophilia in Horn's Archiv for 1820 : he was a professor in the University of Bonn, and the Bonn studentswere thus familiarised with the disease, and for several years after, more cases were published from the provinces watered by the Rhine and the Main, than from any other part of Germany: the Bonn students had become practitioners, and recorded their cases. The influence of Schonlein, also, at Wiirzburg helped in the same direction, as testify the numerous inaugurai dissertations on haemophilia published at Wiirzburg during the time that Schonlein held the chair of pathology in that University. The cases came from the Rhine and the Main so exclusively, that in 1847 ì* could be said that the home of haemophilia was in the vine- yards. But wait another ten or twenty years, and the disease is found to be spread almost equally over Ger- many. The reason of this is plain : the disease has become widely known ; the monographs of Lange, Wachsmuth, and Grandidier, and the descriptions of the disease in the handbooks, especially in Virchow's great work, bave awakened an interest in haemophilia throughout Germany. Reports also come in from Ger- man physicians, living in Russia and the Indian Archi- pelago, countries thought to be free from the dis- ease. Again : My friend Mr. Swanzy informs me that haemo- philia is not an extreme rarity in the hospitals of Dublin ; and yet there are only two Irish cases, so far as I know, on record. In like manner, Dr. Gross, speaking in 1845 JETIOLOGY OF HJEMOPHILIA. 41 of haemophilia, could say that '* almost every practitioner Chap. IH. must bave noticed cases of this description/'^ and yet the United States, since the very beginning of this century, have afforded but one or two cases at the utmost. These facts make the probability great that the number of recorded cases depends not upon the frequency of haemophilia in a given country, but upon the previous education of the medicai men, and the in- terest which they take in the disease. No conclusions either can be drawn from the absence of any description of haemophilia in the books which treat of the climate and maladies of a country.* In the Indian Sanitary Reports it is very unlikely that any mention of the disease should occur ; the statistics are arranged ac- cording to the Nosology recently published by the Lon- don College of Physicians ; and this work does not admit haemophilia into its lists of disease. Another fact, opposed to the idea that haemophi- lia is confined to the Indo-Germanie race, is its prevalence amongst the Jews, a certain percentage of the German cases having occurred in this Semitic nation. The notion that ali bleeders are sprung of a common stock is plainly an impossibility, when the wide diffusion of the disease is considered. ^ Gross, Elements of Patholo- gical Anatomy, Philadelphia, 1845, Sec. Ed. p. 65. « A cruciai instance of this may bere be noticed. Grandidier {pp. cit, p. 46) quotes a work by Waitz, published at Amsterdam in 1843, upon the dise^ses of children in the Indian Archipela- g-o to prove the absence of haemo- philia in that region. In 1859, Heymann {Arch,/. path. Anat, Bd. xvi. p. 182) published an account of a family of bleeders in Suma- tra, in whom the disposition could be traced back for 3 generations. G 42 ^TIOLOGY OF H^MOPHILIA. Chap. III. Haemophilia does not seem to select any one class in ^social life more than another : it occurs in the families of the peer' and the pauper. Most of the recorded cases, as might be expected, come from the middle and lower classes. The geographical distribution of haemophilia has been already discussed : it appears in the low sandy plains of North Germany, and in the Swiss mountains, 5000 feet above the level of the sea, as well as in the valleys and watersheds of the Rhine and the Main. It does not seem to be influenced by food ; since the inhabit- ants of Tenna, where haemophilia might almost be called endemie, live chiefly upon meat and milk ; nor are any hygienic conditions known to bave any share in the generation de novo of the disease. * I bave heard of a case in the thought by some to bave been family of an Englisb nobleman ; tbe subject of tbis disease. and Cbarles IX. of France is CHAPTER IV. SyMPTOMS OF HìEMOPHILIA. The first signs of the presence of haemophilia are, Chap. IV. in nearly every case, given in the period of childhood, that is, from the time of birth to the commencement of the second dentition. Grandidier^ found that out of 65 boys, positive signs of the disease had appeared in 62 before the end of the tenth year. Out of 70 cases, the disease first appeared in 48 towards the end of the first year, the beginning of the first dentition.* Haemo- philia may indeed show itself immediately after birth ; as when a child, born of a bleeder stock, almost bleeds to death after ritual circumcision. Haemorrhage on the falling off of the stump of the umbilical cord is not often seen in haemophilia : out of 185 bleeder families, and 576 individuai bleeders, it occurred in only g families, and 12 individuals.^ Virchow does not give the au- thority upon which he states that bleedings may take place during the birth of the child :* and Nasse's remark, that the disease already exists in the foetus,^ although highly probable, cannot be proved. The disease is latent at the time of birth, but does not manifest itself until provoked by some injury ; and it most usually ' Grandidier, op, cit, p. 91. ^ Virchow, Handh, d, spec, Path, * Grandidier, Schmidt's Jahr- u, Ther, Bd. i. p: 264. bucheri Bd. cxvii. p. 335. ^ Nasse, quoted by Lange, op. 3 Grandidier, Die /reiwtlligen cit, p. 186. Nàbelhlutungen, Cassai, 1871, p. 84. 44 SFMPTOMS OF H^MOPHILIA. Chap. IV. appears about the end of the first twelvemonth, because ^the infant then begins to be put upon its feet, and is allowed to crawl about, being thus exposed to injuries from which it was before protected when carried in the arms. It is not uncommon to find that no symptoms of haemophilia have been noticed until a considerable injury draws attention to the great loss of blood. This is, of course, more common amongthe neglected children of the poor than in the families of their betters. The latest age, at which it has been asserted that haemophilia has first appeared, is between 21 and 22. Both father and son became subject to profuse bleedings first at this age, and both died of haemorrhage.' The joint affections, which are so prominent a feature in typical cases of haemophilia first appear between the commencement and the completion of the second denti- tion, that is, between the 7th and 8th years of life, and the I3th or I4th. Very rarely is the first appearance delayed till after puberty. Persons who are the subjects of haemophilia have often light hair and eyes. Sometimes, however, the hair and eyes are black or dark brown. Their skin is thin and transparent, and the veins are plainly seen. There is nothing Constant as regards their stature or muscular strength. When they are not suffering from the effects of hamorrhage or joint disease, they look well and healthy ; and there is then » Steiner, quoted by Grandi- but the author has chosen to dier, ^/. n7. p. 91. From Grandi- hide his light under the bushel dier's account, neither case seems of an inaugurai dissertation, and to be one, about the diagnosis of I have therefore been unable to which there could be no doubt ; procure or see the originai. SYMPTOMS OF HJEMOPHILIA, 45 nothing by which they may be distinguished from other Chap. IV. healthy persons." Physical examination detects nothing unnatural in the chest or belly : in one or two cases the spleen or liver has been thought to be enlarged,* but this is quite the exception. Grandidier is of opinion that a stronger and more diffused impulse of the heart is common.3 Many observers agree in one point which is, per- haps, the most singular feature of this very interest- ing disease : these patients are often of considerable intellectual capacity ; and it is stated that, as children, they distinguish themselves at school/ ' Otto (^Medicai Repository, New York, 1803, voi. vi. p. 3.) says that "some persons, who are curi- ous, suppose they can distinguish the bleeders (for this is the name given to them) even in infancy ; but as yet the characteristic marks are not ascertained suffi- ciently definite." And Hay: ij^ew England Journal of Medi- cine and Surgety, Boston, 181 3, voi. ii. p. 225) "The great g-randmother of Mr. Hartshorne's children, pronounced them bleed- ers in their infancy ; her predic- tions, with regard to her bleed- ing descendants, have always been verified." Dequevauviller {De la disposition aux Mmorrhagies^ etc, Thèse de Paris, 1844, No. 87, passim) seems to think that a sta- ture of some height, a fine skin, small muscular development, ab- sence of fat, scanty hair, and a transparent sclerotic are always to be found when any disposition to capii lary haemorrhage exists. As a rule, the statement in the text holds good. * Beier, De HcBmophilia^ Diss. Inaug. Berol. 1864. p. 28. "He- patis lienisque volumen auctum." Waterhouse, British Medicai Journal^ 1870, voi. ii. p. 680. The spleen enlarged, liver dimin- ished in size. Schiinemann, Arch, /. path. Anat, Bd. xli. p. 289. Liver and spleen enlarged, post moriem, 3 Grandidier, op, cit. p. 82. 4 Lange, op, ciL p. 202. I feel much inclined to regard this be- lief as a myth : it was first intro- duced by Krimer, who noticed in his patients a great talent for mechanics and music; the ob- servation has been imitated by his successors. 46 SYMPTOMS OF HJEMOPHILIA. Chap. IV. Wachsmuth has pointed out two forms of haemophilia, an erethetic and an atonie form.' Intheerethetic form, the patients bave mostly dark hair, sometimes, however, light ; blue or dark eyes ; delicate white skin through which the veins are clearly seen ; but sometimes there is an increase of pigment in the skin. The figure is often slender, but the muscles powerful ; temperament sanguine ; as a rule cheerful and good-tempered, they are liable to outbreaks of violent passion. Their in- telligence and memory are good, and they are fond of music, drawing, and mechanics. In the atonie form, the patients bave light hair and eyes ; there is little disposition to the formation of pigment ; the constitution resembles that in ' serofula ' ; tempera- ment phlegmatie ; they are indolent and listless, while their mental faeulties are usually below par. The disposition which some authors* bave remark- ed in these patients to occupy themselves with wo- manish pursuits, arises clearly not from the haemo- philia but from the care that their friends take to ward off ali injuries : hence the boys are not allowed to join in the ordinary sports of their age, and this, doubtless, impresses a somewhat feminine character upon them. When they attain puberty, there is often little or no beard, and only a few short hairs on the upper lip ; about the pubes, the hair is as abundant as usuai. The functions of animai life are, as a rule, well performed. Digestion and assimilation seem to be ' Wachsmuth, op, cit, p. 33. « Especially Krimer, Horn's Archiv, 1820, Mai-Juni, p. 409. SYMPTOMS OF HjEMOPHILIA. 47 quite naturai. Two analyses of the urine bave Chap. IV. shown a diminution of the urea and urie acid :' but tbese were both made by the old method of estimat- ing the percentage of urea &c. in a given specimen ; and they do not appear to bave been repeated. Finger found no diminution of the urea in one of bis cases.* There are three well-marked degrees of haemophilia. The first presents the most typical and characteristic form : in it there is a tendency to every kind of baemor- rhage, traumatic or spontaneous, interstitial or super- ficial. The tendency to the swelling of the joints is also well marked. This form is scarcely ever seen in women, but it is by far the most common among men. The second degree of the disease is infinitely less intense ; spontaneous baemorrbages from the mucous membranes only are present ; neither traumatic haemor- ' In Grandidier's case (pp, di. p. 35) of a Jew bleeder, ag-ed 14, the analysis was made by Wild : there was no albumen, sugar, or haematin present. looo parts contained : Water 968792 Urea 1875 Potash Sulphate 2-141 Soda Sulphate 2-083 Soda Phosphate 1-462 Lime & Magnesia Phosphate -674 Sodium Chloride 2-96 Ammonia Phosphate & Chloride 1*92 Extractives -815 Urie Acid '403 In Schliemann's case (quoted by Grandidier, op. ctt, p. 36) of a bleeder, aged 13, the analysis of the urine by Raub in Wurzburg gave the follo wing results : lOOO parts contained : Water 973'88i3 Urea 5'2i5 Potash Sulphate 2*634 Lime Sulphate '0065 Soda Phosphate '274 Lime Phosphate . *io8 Magnesia Phosphate 1*071 Sodium Chloride 5*493 Ammonium Chloride ^'577 Extractives 7*9^9 Mucus '677 Albumen '0007 Urie Acid ;:..:;::;.: •0065 * YmgeVj'Sichxaiài'syahrbucher, Bd. cxvii. p. 330. 48 SYMPTOMS OF HJEMOPHILIA. Chap. IV. rhages, nor ecchymoses are met with ; and the joint afFection is absent, or represented only by rheumatic pains. When haemophilia occurs in women, it usually assumes this forni ; and it may sometimes also be seen in boys and men. The third is the lowest degree of the disease, the liability to spontaneous ecchymoses being the only sign of its presence : it takes this forni only in some members of bleeder families, especially amongst the women, whose menstruation is said by some to be early and abundant. Certain conditions, psychical and physical, appear to cause an aggravation of the haemorrhagic dia- thesis, or even to be the predisposing or exciting canses of haemorrhage. Firstly, psychical : anger and other depressing emotions seem able to cause bleeding, interstitial or superficial, as in Fournier's,' Martin's,* and two of Resal's^ cases. One of Grandidier's pa- tients, also, suffered from haemorrhage when excited.* The influence of the depressing emotions in the genera- tion of haemophilia has been already spoken of, Secondly, physical : and these causes are many. i. DifFerence between day and night. Wachsmuth,* ^ Foumier, Gaz.desHòp. 1851, No. 123, p. 494. * Martin, Jenaische Annalen /, Pkys. u, Med,y Jena, 1850, Bd. ii. p. 312. Quoted by Reinert, Ueber Hàmophilie^ Diss. Inaug. Gòtt. 1869. p. 23. 3 Resal, Quelques pages sur Vhk- mophylie, Thèse de Paris, 1861, pp. 27 and 31. 4 For instance, when in church : but this man was so subject to bleedings that, when he washed his face, he had to be careful net to handle his nose at ali rougfhly lest an intractable haemorrhag-e should come on (See Grandidier, op, ctt, p. 31.) 5 Wachsmuth, op, cti. p. i2. SYMPTOMS OF HJEMOPHILIA. 49 Mutzenbecher,^ and myself,* bave noticedthe appearance Chap. IV. of haemorrhage at night rather than by day. ii. Changes of weather. Krimer,^ Bicking/ Vieli,^ Mutzen- becher,^ Resal/ and Elsàsser^ speak of the appearance of spontaneous baemorrhages in cold damp weather. With Tardieu's^ patient they were very common after ali changes of weather, especially fogs and snow. Great beat and cold seem in some cases to precede the bleed- ing. On the other band, Otte," availing himself of the exact meteorological observations pubJished in the Preussiscke Medicinal-Zeitung, has found little or no relation between the changes of weather and the state of the patient. The appearence of bleedings was in no way influenced by the state of the barometer. iii. The seasons. A large number of observers bave noticed that the bleedings come on more com- monly in autumn and spring, than at any other time. Lange says that the least number of bleedings occur in the summer months." iv. The moon. Krimer," ' Mutzenbecher, quoted by Grandidier, op. a/, p. 97. The children would go to bed appa- rently well, and rise in the morn- ing" covered with ecchymoses. This plainly, however, allows of other explanation. « See the case of James Day, p. II. 3 Krimer, reported by Nasse, Horn's Archiv, 1820, Mai-Juni, p. 418. * Bicking, Hufeland's Journal^ Bd. Ixxxiv. Stùck iv. p. ili. 5 Vieli, reported by Grandi- dier, op, cit, p. 19. ^ Mutzenbecher, quoted by Grandidier, op, cit, p. 96. 7 Resal, op, cit, p. 18. ^ Elsàsser, Hufeland's Journal, Bd. Iviii. Stiick ii. p. 98. 9 Tardieu, Arch, gén. de Méd. 1841, février, p. 187. " Otte, Ueherdie Bluterkrankheit, 1 865, Leipzig, p 31. Moreobserva- tions of this exact kind are wanted. II Lange, op, cit, p, 194. » Krimer, op, cit, pp. 4 1 2 and 420. H so SYMPTOMS OF HJEMOPHILIA. Chap. IV. and one or two observers after him, bave fancied tbat '^' tbey detected a relation between tbe increase of the moon, and the appearance of hamorrbages. v. The use of wine. Dequevauviller noticed haemorrhage to foUow the use of wine, whenever the patient took it.' vi. Some bave thought tbat the disposition to bleed is greatly aggravated after the first traumatic haemor- rhage. Tbe symptoms of b^mophilia may be considered under three beads : tbe bleedings, wbether traumatic or spontaneous ; the ecchymoses and petechiae ; the pecuHar joint affections. I. The bleedings are very common, occurring up- on the slightest, or no, apparent cause, sometimes last- ing for days or weeks : tbey are often extremely profuse, and most difficult to arrest. i. Spontaneous bleedings. These are sometimes preceded by prodromata ; sometimes not : and this variability occurs in the same individuai at different times. Tbey are uncommon in the second degree of the disease. The prodromata occur from 3 to 4 days before the onset of the haemorrhage. There are signs of great plethora: tbe face full; tbe lips swoUen and red ; tbe ears red and hot ; a frequent full pulse ; beatings of the heart and carotids ; dyspnoea ; tbe skin hot to band ; headache and giddiness ; the urine scanty and high- coloured, and the bowels confined. Sometimes there are darting pains in the liiiibs. There are often symp- ' Dequevauviller, De la disposition aux hémorrhagies^ Thèse de Paris, 1844, No. 87, p. 36, SYMPTOMS OF HJEMOPHILIA. Si toms which indicate the part which is about to bleed ; Chap. IV. such as a pain in the back when haematuria is coming on ; or an itching in the nasal cavity before epistaxis.' Wachsmuth* points out the psychical prodromata, and says they differ in the child and the adult. In the child there is usually great cheerfulness and liveliness ; occa- sionally the reverse, listlessness ; the child is very talk- ative, and incHned to a laughter which has something spasmodic in it. It is easily made angry, and then often bursts into violent crying ; and it is easily fright- ened. In one case, epileptiform convulsions have been seen.3 There is increased sensibility of hearing and sight. In the adult, there is a certain amount of good temper, accompanied by a marked restlessness. There is great sensibility which readily passes into angry ebullitions. The person becomes timid, and the speech quick. There is an increase in the sexual appetite. AH these symptoms disappear within a short time after the selting in of the haemorrhage. I have never been fortunate enough, in the cases which have come under my notice, to see the prodro- mata described above. It would be interesting to com- pare the temperature of those parts, the cheeks, the ear, which feel so warm to the band, with the tempera- ture of the axilla or rectum : it might be well also to ^ Otte has noticed a great based chiefly upon observations hunger to come on a few hours made in his own family, so that before the occurrence of epis- they must not be too hastily gen- taxis ( Ueher die Bluterkrankheity p. eralised. 4.) 3 Beier, De Haemophilta, Diss. 2 Wachsmuth, op, cit, p. 15. Inaug. Berol. 1864. p. 26. The description seems to be 52 SYMPTOMS OF HJEMOPHILIA. Chap. IV. note the state of the pupils, and the increase or diminu- tion of the salivary secretion. According to Wach- smuth, an increase of this secretion is not uncommon before a bleeding from the mouth.' After these pro- dromata have lasted from 3 to 4 days, or, in those cases in which prodromata are absent, without any warning, the bleeding begins. These spontaneous bleedings come most commonly from the mucous membranes, very rarely from the skin, serous mem- branes, or within the cranium. The reason of this is obvious ; the vessels of the mucous membranes are less supported than those of other parts. In childhood, these persons more frequently bleed from the nose than from any other part. Few of them live to any age without sufFering from it ; and it appa- rently occurs indifferently out of either nostril. The next most frequfent place of bleeding is the mouth : and in the mouth, the gums are the most predisposed to bleed ; indeed some of these patients are unable to clean their teeth with an ordinary tooth-brush without draw- ing blood. The entire mucous membrane of the mouth may supply the blood ; or only a part, as the lips and cheeks. A loose rough tooth will often cause bleeding. Bleeding from the gums usually occurs at the time cf the first or second dentition. After puberty, bleeding from the nose and mouth becomes less common, and is replaced very often by haematuria, or by bleedings from the bowel. Vomiting of blood and haemoptysis become more common. It is less usuai to have spontaneous bleedings from the ^ Wachsmuth, op. at. p. 15. SFMP TOMS OF HJEMOPHILIA. 5 3 genital organs, male or female ; and very rare from the Chap. IV. ears or caruncle of the eye, from the ends of the fingers or hairy scalp, or into the serous cavities. Grandidier gives the foUowing numbers of locai bleedings in 256 cases :^ from the nose, 122 ; from the mouth, 34 ; from the stomach, 11 ; from the bowel, 33 ; from the urethra, 13 ; from the lungs, 15 ; from the end of the fingers, 4 ; from a swoUen place on the scalp, 4 ; from the tongue, 4 ; from the ear, 3 ; from the eye-lids, I ; from the female genital organs, io. The amount of blood lost from these spontaneous bleedings varies very greatly : it may he but a few ounces, or it may be so great that the patient shall die. The spontaneous bleeding most commonly fatai is epis- taxis ; less frequently, bleeding from the mouth, bowel, or lung. There is only one case on record of death from haematuria.* Resal has pointed out two forms of spontaneous haemorrhage, which are, however, best marked in the second degree of this disease. In one, the haemorrhages are small in quantity, but frequently repeated ; they occur without prodromata, and always from the same mucous surface ; they produce no constitutional efFect. In the other form, there are often prodromata lasting three or four days, and the haemorrhage is great in quantity, and has little tendency to be arrested spon- taneously.3 ' Grandidier, Schmidt's Jahr- 3 Resal, Quelques pages sur Thè- biicher, Bd. cxvii. p. 332. mophylie, Thèse de Paris, 1861, * A case of Vieli's, a boy 8 No. 150, p. 48. years old (Grandidier, op, cit. p. 27). 54 SYMPTOMS OF HJEMOPHILIA. Chap. IV. It sometimes happens that when one haemorrhage ceases, another comes on, until at last the patient dies exhausted. Or the same haemorrhage may con- tinue, with varying intermissions, until the death of the patient. The spontaneous bleedings sometimes alter- nate with the swellings of the joints. ii. Traumatic bleedings. In some cases of haemo- philia, especially when the patients belong to the female sex, excessive bleeding does not take place when a part is wounded. And in some bleeders a wound will at one time be foUowed by bleeding that scarcely exceeds what is naturai ; at another, the same kind of wound will cause a haemorrhage that cannot be checked. AH vas- cular parts of the body may bleed furiously when injured, but the bleedings seem to be particularly dangerous when ecchymoses or haematomata are wounded. The smallest hurt is often sufficient to set life in danger ;' a prick, a scratch, or cut, which another person would scarcely know had been inflicted. Death from bleeding has occurred after su eh slight wounds as the division of the fraenum of the tongue,* the scarifications necessary * The circumstances of one or two of the most striking cases may be here mentioned. A stu- dent, aged 22, received in a duel a cut on the face, 2 inches long, and 3 lines deep. Notwithstand- ing the use of every conceivable styptic, he bled continuously, and died on the 4th day. (Escherich, Henke's Zeitschrìft fur die Staats- arzneikunde, 1847, Bd. liii. p. 18.) A lad, aged 20, had an appiè fall upon his nose : thereupon bleeding that could not be stop- ped, and death in 24 hours. The brother of this boy, being bled for pleurisy, died of haemorrhage from the incision, consequent gangrene of the arm, and am- putation. (Donkersloot, Nedet- landsch Lancet, 1850, p. 419.) * Rieken, Neue Untersuchungen SYMPTOMS OF HJEMOPHILIA. H for vaccination,^ the application of leeches, or the ex- Chap. IV. traction of a tooth. This last is an especially common cause of death, and ought never to be undertaken in a patient with this disposition. But these patients difFer very much in the amount of handhng that they will bear. In one family, venesec- tion may be done, or cupping glasses applied, without much difficulty in stopping the bleeding: while in another, even the appHcation of blisters may be in the highest degree dangerous. I bave seen a tooth drawn without any remarkablehaemorrhage: few operations are more dangerous. A small superficial hurt, especially if torn or lacerated, is thought by some* to be more dangerous than a deep clean-cut wound. Wachsmuth says that the proportion of dangerous bleedings, caused by blunt instruments, is to those caused by sharp in- struments, as 5 : i.^ It must not be forgotten, however, that, in nearly ali the cases of surgical interference for the arrest of the haemorrhage, the wound made by the knife has bled as furiously as the originai injury .-* The in Betreff der erhlichen Neigung zu this statement : but there is no- tddtlichen Blutungen^ Frankfurt a. thing whatever in his descrip- M. 1829. p. 14. i\on (Fragmenta chirurgica et medica, Wardrop, On Blood-letting, p. 41) which warrants such an London, 1835, p. 18. Three assertion. cases reported by Ward. ^ Wachsmuth, loc, di, ^ Henschel, reported by Gran- 4 Lafargue, Revue Mèd. 1835, didier, Schmidt's Jahrhucher, Bd. t. iv. p. 92, cxvii. p. 331. Lebert, Arch, gin, de Méd,, ^ Wachsmuth, e?^. ciU p. 23; and 1837. sept. p. 40. Allan, Monthly Journal, 1842, Thal, Kleinert's Repertorium, pp. 501 and 503. Fordyce is 183 1, Mai, p. 123. frequently quoted in support of S6 SYMPTOMS OF HjEMOPHILIA. Chap. IV. explanation of these two contending statements probably lies in the fact that the disposition to haemorrhage varies so greatly at difFerent times in the same person ; that a wound, whether clean-cut, or otherwise, may be made at one time without much risk ; whilst at another, when the disposition to bleed is at its high- est, the very means that the surgeon uses to stop the bleeding elsewhere, become a fresh source of loss of blood. Vaccination, as a rule, may be done with safety : there is only one case on record, in which it is even doubtful if the child were the subject of haemophilia,' in which death has foUowed this small operation. There is also another case in which dangerous bleeding fol- lowed the insertion of the vaccine matter into 4 punc- tures :* nevertheless, the vaccination succeeded. Rieken' seems to think that the vaccination of a bleeding part might be useful in stopping the haemorrhage. Be this as it may, in ali the other cases where the fact is noticed at ali, it is said that the vaccination ran its usuai course. Hughes has described a family in whom the applica- tion of blisters '*drew blood instead of water;''* and says that he has seen death occur twice from this cause. ' A little girl aged 3 months, suffering from whooping-cough, among whose relations no ac- count of a disposition to bleed could be obtained, died in a few days after vaccination, of bleed- ing, not only from the scarifica- tions, but also from a place on the nose which the child had scratched. (Henschel, Schmidt*s Jahrhucher, Bd. cxvii. p. 331.) a Heyfelder, Medicinische Zei- tung (Vereins), Berlin, 1833, p. 216. 3 Rieken, op, cit, p. 1 16. 4 Hughes, American Journal of Medicai Science, 1833, voi. xi. p. S42. SYMPTOMS OF HJEMOPHILIA. 57 Usually, however, blisters are foUowed by nobadresult, Chap. IV. even when suppuration is set up. If abscesses be opened, either by the surgeon or of themselves, a profuse bleeding usually takes place. Stili more profuse is the bleeding when a blood tumour or extravasation of blood is wounded, and the haemorrhage is only to be stopped with great difficulty. Those wounds which are not attended by great haemorrhage usually present nothing unusual : those, however, which bleed so greatly, rarely heal by the first intention. They very often suppurate ; and sloughing is not uncommon. When the wound begins to suppu- rate, the haemorrhage usually stops : but even then the patient is not secure ; for after the wound has apparently healed, the bleeding may burst out again after a few days : and this alternation of healing and bleeding may go on for several weeks. The bleeding, whether spontaneous or traumatic, is almost always capillary. The blood oozes out of the part continuously, without any distinct rise or fall : no bleeding points can be seen, but the blood trickles out as if pressed from a sponge. In Blagden's case, a bleeding artery was seen and secured ; but the vessel, from the thinness of its coats, soon gave way/ In the cases where amputation has been done, or the vessel tied in its length, there is no mention of any difficulty in securing the arteries.^ ^ Blagden, Med.-Chir, Trans,, carotid in an attempt to stop the voi. viii. p. 225. An artery on bleeding after the taking out of the forehead was bleeding*. Some a tooth. years after, Sir B. Brodie tied the * Clutterbuck, Lancet, 1826, I 58 SYMPTOMS OF HJEMOPHILIA. Chap. in. A bleeding may last only a few hours, or for i8 weeks.' In the first instance, the loss of blood in so short a time may be so great, that the patient shall He as if dead, be pulseless, and blanched. The shortest time on record, between the first occurrence of fatai bleeding . and death, is six hours ; a boy aged 3 was cut for the stone in Guy's Hospital about 2 o'clockin the aftemoon, and died the same night at half-past 8.* Epistaxis has proved fatai in 24 hours,^ and a bite of the tongue in an infant in 36 hours/ Very commonly profuse bleeding does not immediately foUow the infliction of the wound; but the bleeding Comes on a few hours, or it may be a day or two, after the hurt has been given. The quantity of blood lost in a very short time may be enormous ; but this rapid loss of blood does not seem Aprii, p. 99. A limb was ampu- by a cut, and tied after the hae- tated, and the patient died of the morrhage had lasted for two continuous oozing from the days. stump. Sentex, Mèmotres de la Soc, mkd.* Lebert, Arch. gèn, de Mèd,, 1837, chir, de Bordeaux, 1866. t. i. p. 3 1 1 . sept. p. 40. The radiai and bra- The brachial was tied for a crush chial arteries were tied. of the forearm. Donkersloot, Nederlandsch Lan- i Uhde, Deutsche Klinik, 1850, cet, 1850, p. 419. Amputation of p. 540. This man usually bled the arm was done for gangrene for three or four weeks after any foUowing the incision for phleb- trifling accident otomy. * Durham, Guys Hospital Re-- Lafargue, Revue mèd,, 1835, ^r/f, 1868, voi. xiii. p. 490. t iv. p. 92. The crural artery 3 Donkersloot, loc. cit. was tied. * Theinhardt, reported by Wilmot, DuUin Journal of Med. Nasse, Hom's Archiv, 1824, Juli- Science, 1841, voi. xix. p. 234. August,p. 121. The linguai artery was divided SYMPTOMS OF HJEMOPHILIA. 59 to be so dangerous as longer continued, frequently Chap. IV. recurring, smaller bleedings. Schafer's patient lost by spontaneous bleeding from the mouth, chiefly the gums, three or four pounds of blood in 24 hours :' one of Krimer's lost, after the taking out of a tooth, three and a half pounds in the same time.* The medicai student, whose case has been recorded by Coates, also had a tooth taken out, and in less than 24 hours, half a gallon of blood had been poured out : the bleeding lasted io days, and the entire quantity of blood lost was estimated at not less than three gallons.^ In the younger Thore's case of a boy of 5 years old, nearly a pound of blood was lost on two occasions from a very small wound/ In Miller's case, 5 or 6 pounds of blood were lost in 36 hours from the gums.^ Liston was the first to make observations on the composition of the blood in this disease.^ After assert- ing that it was deficient in fibrin, and that the globules were broken down or diffluent, he says '*the blood was altogether in a bad state, containing a proportion of globules with ali the characters of those entering into the composition of pus, "7 But leaving these, and similar * Schàfer, Medizin, Zeitung ( Ve^ reins), Berlin, 1836, p. 130. * Krimer, reported by Nasse, Hom's Archtv, 1820, Mai-Juin, p. 416. 3 Reynell Coates, North Ameri- can Medicai and Surgical Journal, Philadelphia, 1828, voi. vi. p. 45. * Thore, Gaz. mèd, de Paris, 1856, p. 653. ^ Miller, Edinburgh Medicai journal, 1856, Jan. p. 638. ^ Nasse, as well as Meckel, had previously directed attention to the state of the blood. (ReiFs Arch. /, d. Phys.y 181 1, p. 266; and Deutsches Arch, /, d, Pkys, 18 16, Bd. ii. p. 138.) 7 Liston, Lancet, 1839, Aprii, P. 137. 6o SYMPTOMS OF HJEMOPHILIA. Chap. IV. inexact observations,* the attempts at chemical analysis will present more interest. At the very outset a con- siderable difficulty presents itself: our knowledge of the chemical composition of the blood, even at the present day, is not so perfect that much light can be expectéd to be thrown upon the pathology of haemophiHa by the help of chemistry. The older analyses differ among themselves : in Heyland's analysis the blood contained a considerable excess of fibrin, 5 per mille.* In Wachs- muth's case, nothing unnatural could be discovered :^ while in Tardieu's case, the blood was found to be deficient in fibrin and cruor; its density much di- minished ; and six hours after the blood was drawn, it had not coagulated.* But the examination does not seem to bave been very carefuUy made. Analyses of the blood in haemophilia bave been made within the last io years by three observers. There is an analysis by Ritter, reported by Gavoy,^ of the blood ^ Such as Rogers' statement, reported by Otto {Medicai Reposi- tory, New York, 1803, voi. vi. p. I.) that the blood " seemed to be in a high state of eflervesence." * Heyland, quoted by Lange, op, cit. p. 198. The analysis is : 780 of water, 5 of fibrin, 70 of albumen, and 137 of cruor, in 1000. 3 Wachsmuth, op, cu, p. 16. The analysis was made by Dr. Duflos ofBreslau: an ounce of blood from the nose was exam- ined. 4 Tardieu, Arch. gèn. de Mèd. 1841. févr. p. 190. He does not give numbers: the blood was fumished by the operation of phlebotomy, which was conducted 8 days after a bleeding from the gums had ceased, which bleeding* lasted 4 days. Another analysis, made six months afterwards, con- firmed the results of the former. 5 Quoted by de Fleury, Mhn. de la Soc, méd,-chtr. de Bordeaux, 1866, t. i. p. 306. I regret very much that I bave been unable to procure Gavoy's originai publica- SFMPTOMS OF H^MOPHILIA. 61 of a boy, aged 14, who died in a hospital at Strasburg. Chap. IV. There was found : Water 92*320 Fibrin '264 Albumen 7*390 Salts -026 In the second analysis : Water 92*244 Fibrin '264 Albumen 7*470 Salts '022 Otte, following Scherer's method, analysed the blood of bis patient ; nearly a pound of blood was lost in 5 hours from the nose ; no haemorrhage having taken place for 15 daysbefore ; nothing unusual was noticed about the coagulation. The specific gravity of the serum was 1*029. The estimation gave the following results :^ Water 905*04 Albumen 79'S4 Fibrin 4-35 Fat 1-82 Soluble Salts 5-43 Extractives 3*82 Leconte analysed some blood, furnished by an epis- taxis, from a woman sufFering from the second degree tion. It would seem that the ' Richard Otte, Ueber die Blu- blood analysed was lost from the terkrarikheit^ Leipzig, 1865, p. 23. nose. 62 SFMPTOMS OF HJEMOPHILIA. Chap. III. of haemophilia.' The coagulum was well formed and resistant, the serum properly separated and limpid, and the corpuscles showed no alteration under the micro- scope. The blood contained 14* 1464 per cent, of dry residue, which consisted of : Fibrin '1654 Albumen 7*5080 Corpuscles 6*4730 A second analysis, not completed, made six months later, gave 14*540 per cent, of dry residue. In a few days, a third analysis was made and gave the foUowing results ; Fibrin '2000 Albumen 7'SOOO Corpuscles 6*2590 Water 860410 It will he observed at once that these analyses have failed to discover any unnatural state of the blood. They were aU, hqwever, made without any attempt at a distinction of the constituents of the plasma and the corpuscles : and greater attention might have been paid to the amount of inorganic salts. It is very probable, however, that in nearly ali cases, no chemical alteration of the blood would be discovered. Most of the earlier writers state that the blood does not coagulate. According to recent observations, the truth seems to be that the blood at first coagulates naturally ; but that after a great deal has been lost, it coagulates feebly, or not at ali. The blood is then so thin that it resembles water in which fresh meat has been washed, and scarcely stains linen. Chemical » Leconte, reported by Rasai, Quelques pages sur Vhhnophylie^ Thèse de Paris, 1861, p, 56. SYMPTOMS OF HJEMOPHILIA. 63 examlnation of the blood in this state seems to be quite Chap. IV. wanting. . It is somewhat surprising, considering the ease with which microscopical examinations of the blood cor- puscles can be made, that so few should be at present recorded. Uhde,' Finger,* and Resal^ found nothing unnatural in the shape or appearance of the corpuscles : Finger, however, thinks that there was an undoubted increase in the relative number of the red corpuscles in about 4 or 6 days after the beginning of the bleeding, together with a complete disappearance of the colour- less corpuscles : when the bleeding had lasted a longer time, the blood becoming less red, and the coagulum less firm, there was a decrease of the red, and a slight increase of the white, corpuscles. Dr. Moxon found after death an increase of the white corpuscles, when the bleeding had lasted only six and a half hours/ In Tardieu's^ case, the corpuscles were regular in shape, but the nucleus {sic) was pale, transparent, and ill- formed. The few facts at our command seem to point to no unnatural state of the blood in haemophilia ; the changes, which take place in the blood after successive bleedings bave occurred, are probably due to the rapid loss of the ^ Uhde, loc, di, a Fing-er, Schmiòi* syahrhiiciier, Bd. cxvii. p. 330. 3 Resal, loc, ctt. * Durham, loc, ctt. An increase in the amount of white corpus- cles is usually observed after hae- morrhage. Schiinemann (Arch, /. path. Anat, Bd. xli. p. 289.) found the blood, after death from long-continued bleeding* from the socket of a tooth in a young- man of 21, to be watery and to contain fewer red corpu- scles : but he makes no mention of the white corpuscles. 5 Tardieu, loc. cit. 64 SYMPTOMS OF HMMOPHILIA. m Chap. IV. fluid, and can scarcely be ascribed to the disease. Chemistry and the microscope bave hitherto done but little in the discovery of morbid states of the blood in other diseases attended with a haemorrhagic diathesis, as scurvy and purpura ; and it seems unlikely that they will prove of much assistance until our knowledge of the naturai composition of the blood bave been much enlarged. The prodromata which bave been spoken of above as preceding the spontaneous bleedings, are continued for a short time after the haemorrhage has begun ; but when the plethora of the vascular system has relieved itself, these symptoms, as might be expected, disappear. The bleeding, spontaneous or traumatic, when exces- sive, can seldom be at once checked by any means hitherto recommended. Sometimes the bleeding does not cease until the patient faint ; and even then there is a danger of a renewal of the haemorrhage on the return of consciousness. Either after one profuse haemorrhage, or, as is more common, after a series of bleedings, interrupted by short intervals, ali the symp- toms of true anaemia show themselves. The pulsa becomes rapid, small, and compressible : if the bleeding bave been great, it may not be felt at ali, and the im- pulse of the heart may become scarcely perceptible. There is a murmur with the first sound at the base, prolonged iuto the great arteries, and the venous hum in the veins of the neck. The face becomes blanched, almost transparent, like a piece of bleached wax : this appearance is very noticeable in the ears and tongue, and is so peculiar, that those who bave once witnessed it, cannot fail to bave been struck by the sight. SYMPTOMS OF HJEMOPHILIA. 65 Should the bleeding continue, the pulse, and impulse Chap. IV. of the heart, can no longer be perceived ; the blood which flows resembles coloured serum or bloody water rather than blood ; delirium and hallucinations, or exaltations of the special senses with retention of con- sciousness, foUow ; and general convulsions usherin the fatai termination. Should, however, the result be favourable, the patient lies long, as in a deep sleep ; and awakes to suffer from a most profound anaemia. When the blood from the nose or mouth has been swallowed, a gastro-intestinal catarrh is often set up ; or coagula of blood in the intestine may cause great pain and trouble in passing. The same difficulty may arise after extreme haematuria, though this form of bleeding seldom causes danger to life. The blood lost is only very gradually regained. The patients look anaemic for four or six months after a great bleeding. The statement that they quickly pulì up again is not correct. In a few cases, depraved appetite, like that shown by chlorotic women, has been observed. The two brothers Buel noticed this in two boys in the same family, after haemorrhage : one had a tendency to eat sand ; the other, common earth.'^ Gintrac alsó speaks of the avidity with which one of his patients swallowed small pieces of stone ;* he had thus destroyed the wall against which his bed was placed. In the last half year of the life of one of Elsàsser's patients, aged 3, he showed a disposi- * W. and S. Buel, London Medi- * Gintrac, Cours théon'que et cai and Physical J oumal^ 181 8, voi. clinique de Paihologie^ Paris, 1853, xl. p. 430. t. iii. p. I IO. K 66 SYMPTOMS OF HJEMOPHILIA. Chap. IV. tion to swallow sand and spice, even directly after ^meals. After bleedings, he liked cold food.' Wil- mot's patient, a boy aged six, showed a strange de^ sire to eat day and lime, and bis bowels were generally very irregular.* II. The petechiae and ecchymoses of haemophilia represent an interstitial form of haemorrhage ; like the external bleedings, they may be either spontaneous or traumatic. i. In those cases where they are present, spontaneous ecchymoses are often the first signs of the disease. With some exceptions, they usually appear in the first year of life ; but their presence is not so Constant as the external bleedings. They are mostly situated in the connective tissue under the skin : at least, this is the place where they are most commonly seen ; for no means exist by which, during life, their presence in the connective tissue of internai organs, such as the peri- cardium or pleura, can be ascertained.^ Wachsmuth says that they are most common on the external parts of generation, and on the buttocks in infants.^ Lange agrees with this,^ and adds that the face usually es- capes. The spontaneous ecchymoses vary in size, being usually small, from a pin's point or head, which is common, to a halfpenny ; larger than this bave not been seen. ' Elsàsser, Hufeland's Journal^ serous membranes are not un- 1824, Bd. Iviii. Stiick ii. p. 99. common in other diseases where * Wilmot, Dublin Journal of a hsemorrhagic diathesis is pre- Medical Science, 1841, voi. xix. p. sent. 239. ^ Wachsmuth, op, cit,, p. 25. 3 Small ecchymoses under the ^ Lange, op, cit,^ p. 215. SYMPTOMS OF HJEMOPHILIA. 67 It is not at ali rare to meet with cases of haemophilia Chap. IV. in which the spontaneous ecchymoses are altogether absent. And, on the other hand, the ecchymoses some- times occur when the external bleedings are absent ; they then represent a less intense form of the disease, common amongst the near relations of bleeders, especi- ally the women. The appearance of these ecchymoses does not seem to depend upon any time of day or season of the year ; sometimes they alternate with external bleedings or swellings of the joints, or are the forerunners of hae- morrhage. ii. The traumatic ecchymoses are caused by extern- al force, usually injuries or blows which would produce no such effect in a healthy person.' They are, accord- ing to Wachsmuth, rare on the trunk ; he says that they are most common on parts removed from the heart, such as the head and face, nates and extremities ; their favourite situation is the hairy scalp.^ A slight degree of this tendency to traumatic ecchy- mosis is by no means uncommon in delicate women. These ecchymoses are usually larger than the spon- taneous ; in fact there is no limit to the extent that ^ In Allan's case, {Monthly Joumaly 1842, June, p. 503) the occupation of the lad was a writer, and the left arm was black from the elbow to the wrist from pressure upon the desk ; also a black line across the belly from the same cause. In Lafargue's case {Revue medicale, 1835, p. 91) a little girl struck a bleeder, aged 41, with her elbow upon the lower part of the arm: there- upon the arm swelled enormously with blood up to the axilla. * Wachsmuth, loc, di. 68 SYMPTOMS OF HJEMOPHILIA. Chap. IV. they may attain : they may fili the connective tissue of a limb with blood ;' or more, cause death by haemor- rhage into the connective tissue generally.* The spontaneous ecchymosis is often preceded by the symptoms of congestion and plethora, with pains in the limbs, which bave been described above as the pro- dromata of the spontaneous external bleedings. When formed, the ecchymoses do not differ from those seen in other diseases attended by a haemorrhagic diathesis, or from those which are the result of bruises. They are of a deep purple or reddish blue colour ; and when dis- appearing, they show the usuai play of colours, green and yellow, which attend the absorption of effused blood. Sometimes they are painful ; at other times not, even upon pressure. If they should be opened by accident, bleedings most alarming and difficult to stop almost invariably foUow.^ In connection with the traumatic ecchymoses must be mentioned the so-called blood tumours. These are to be distinguished from the extravasations of blood into the connective tissue generally of a limb, just as an cedema is to be separated from a coUection of fluid in a * Sir William Jenner used to mention, in his lectures, a case in which the fall of an india rubber air ball upon the thigh had fìlled the connective tissue of the limb with blood from the knee to the trochanters. * Mutzenbecher (quoted by Grandidier, op, ci't. p. 72.) re- cords a case where a child, whose ag-e is not stated, died in consequence of the bleeding* into the connective tissue, foUow- ing- a fall upon the chest. 3 In a case spoken of by Wil- mot {Dublin Journal of Medicai Science, 1841, voi. xix. p. 237.) death occurred from the hae- morrhage follo wing- the opening* of an ecchymosis. SYMPTOMS OF HJEMOPHILIA. 69 cyst. It has been stated by a writer,' who has had Chap. IV. large opportunities for observations, that the blood tu- mours sometimes arise spontaneously ; and, by another, as a consequence of mental emotion :* but it seems very probable that in the instances mentioned they were due to some slight injury that had been forgotten. In the great majority of cases, a blow or injury precedes their appearance : and a slight injury may cause a large tumour.^ The size of the tumours may reach to that of an adult's head/ The skin over them is black or black blue, surrounded by a zone of red. The temperature to the band is sometimes raised, and the surface is usually tender. The tumours disappear slowly, with the usuai play of colours. They very rarely suppurate. Rieken^ felt within one of these tumours an inelastic solid body ; and Hopf,^ on opening a similar tumour in » Viali, quoted by Grandidier, op, cit, p. 70. * Fournier, Gaz. des Hòp, 185 1, No. 123, p. 494. 3 A man, aged4i, fell against the key of a door : soon after, a tumour formed on the right side of the abdominal walls, be- gfinning- at the level of the i ith rib, and extending to the superior iliac spine; it was six inches long, three broad, and two high. (Lafargne, Revue medicale^ 1835-, p. 89.) 4 Thormann, Gràfe und Wal- ther' s Journal der Chirurgie^ 1840, Bd. XXX. p. 298. Three days after a blow from the foot of a cow, a swelling as large as a man's head appeared in the scro- tum of a bleeder, aged 23. Also Vieli (reported by Grandidier, op, cit, p. 23) describes an enor- mous blood tumour in upper part of right thigh. 5 Rieken, Neue Untersuchungen in Betreff der erhlichen Neigung zu todtlichen Blutungen, Frankfurt a.M. 1829, p. 28. ^ Hopf, quoted by Grandidier, op, cit, p. 71. The tumour re- sembled a gouty deposit and was opened by caustic ; about 24-30 ounces of a brown red fluid es- 70 SYMPTOMS OF HJEMOPHILIA. Chap. rv. a bleeder aged 50, found concretions not unlike gall- stones. Coagula of blood not unfrequently become calcified ; a familiar example of this is seen in the phle- boliths so commonly found in the pelvic veins, having their origin in the calcification of thrombi. III. The subjects of haemophilia are prone to an affection which is oftentimes far more distressing and vexatious than the attacks of haemorrhage. The joints, especially the larger joints, bave a disposition to become painful, swoUen, and fiUed with fluid. This disorder is continually recurring, so that some patients are scarcely ever free from it, and they are cripples for the greater part of their life.' The large joints are those most commonly attacked, the knee being the joint which suff'ers most ; the ankle, elbow, shoulder, and hip being seized upon more rarely, and, in the same patient, at longer intervals. The joints of the wrist, and of the fingers and toes are but seldom swoUen. The joint affected becomes swoUen, often suddenly. Sometimes the swelling attains a great size, and the knee of a child may become as large as an adult's head. The swelling is attended by great pain, which increases towards evening ; and by fever, which may be so great that the thermometer in the axilla may rise to 104° or io5°F. The skin over the swelling is warm to the band, but never reddened ; it is much stretched, and caped, of the consistence of a to discharge, the fluid at the end thin syrup, very like that of the resembhng coffee grounds, until pulp of tamarinds, and mixed the patient's death from collapse. with black red, shining, polished ' As in the cases of Bickell concretions, looking like gali- and Robins, pp. 3 and 14. stones. The tumour continued SYMPTOMS OF HjEMOPHILIA. 71 some observers bave from tbis circumstance described Chap. IV. tbe swelling as bard. It bas ratber a soft, somewbat fluctuating feel, and tbe ends of tbe bones forming tbe joint can rarely be felt. Movement, as a rule, increases tbe pain ; sometimes, bowever, passive motion may be borne. Tbe lengtb of time wbicb tbe swelling lasts is very uncertain : as a rule it lasts longer in tbe larger joints. Sometimes it disappears in a few days ; or lasts many weeks or montbs. It may disappear in one joint, only to reappear. in anotber ; or tbe swellings of tbe joints may alternate witb baematuria, or some otber form of baemorrbage.' Wben tbe swelling is gone, tbe joint may completely recover, or tbe ends of tbe bones may be enlarged, and more or less permanent impair- ment of motion may be left. Tbere is always a great liability to recurrence of tbe disease in tbe affected joint, and during convalescence tbere is always great risk of a relapse. Tbe causes of tbe swelling may be eitber traumatic or idiopatbic. Tbe traumatic origin of tbe swelling bas been denied.* But I tbink I bave seen cases wbere sucb a source seemed to be tbe only possible one. Tbe patients bave been in excellent bealtb, tbe weatber bas been mild or warm, a blow or otber injury bas been re- ceived, and in 24 bours tbe joint injured bas been swoUen and painful. Tbere is, also, often a black or blue spot of extravasated blood near tbe joint. Tbese ' Otto Weber, v. Pitha u. where the pain in the knee was Billroth's Handh. d. Chirurgie, suddenly relieved by an abundant 1865, Bd. i. Abth. i. Lief. i. p. 129. bleeding from the nose. Gròschner (Rusfs Magaztn, Bd. * Lange, op, ctt, p. 211. xxxvi. p. 397) relates two cases 72 SYMPTOMS OF HJEMOPHILIA. Chap. IV. circumstances point very clearly to the possibility of a traumatic origin of the swelling. On the other hand, there can be no doubt that the most common cause of the swellings is exposure to cold, or the occurrence of cold damp weather. Thus they are most frequently seen at the beginning of the spring, or end of the autumn. Sudden changes of weather, as from frost to thaw, bave a great influence in producing them. AUied clinically, and probably also pathologically, to the sweUings of the joints, are the pains felt in the limbs, especially about the joints. These pains are often sa severe that they disturb the function pf the limb, making the patient walk with difficulty. The pains are sharp' and usually increased towards night, and, like the swellings of the joints, often foUow exposure to cold and damp, especially in the spring and autumn : in like manner they may also alternate with the spontaneous interstitial or superficial hasmorrhages ; or the pains may form part of the prodromata of haemorrhage. * In some of Vieli*s cases, these pains usually lasted about 9 days ; pains set in with great violence and then left the knee or ankle, and suddenness, and the patients swollen, and blue. See Gran* were so weakened thereby that didier, op^ ctt, p. 73, they had to keep their bed : the CHAPTER V. IdIOSYNCRASIES OF HìEMOPHILIA. In the last chapter, the ordinary sym5^oms of hae- Chap. V. mophilia were discussed, It is now proposed to speak of the peculiarities which the disease exhibits, either in its own progress, or in influencing the occurrence and progress of other diseases, Murmurs over the heart and great vessels have been noticed by several observers : they are such murmurs as are caused by a poor and watery state of blood. An increased and diffused impulse of the heart has also been several times recorded.' These phaenomena about the heart have nothing to do with the pathology of hae- mophilia : they are due solely to the condition of blood. In four cases, already mentioned,* there has been, after haenaorrhages, a depraved appetite for day, sand, earth, &c., similar to the pica of chlorotic and pregnant women. Some authors mention a great sensibility to cold, especially to damp cold : this tendency was shown in its highest degree in a family described by Bicking. In dry weather, the father was quite well, but he feared the cold as an unavoidable souf©e of illness. The son was a perfect hygrometer,^ ' Grandidier op. ctt, p. 82. ^ 3 Bicking-, Hufeland's Joumai, 2 See p. 65. -^Bd. Ixxxiv. Stiick iv. p. in. L 74 IDIOSYNCRACIES OF HjEMOPHILIA. Chap. V. In some few cases, haemorrhages have followed the use of mercury. Burnes' found that on taking blue pili, profuse haemorrhages from the gums and nose occurred ; and this symptom returned again when the blue pili was repeated. Bicking^ found that calomel was ili borne in the family under his observation ; it once c'aused bloody stools and vomiting. Elsàsser^ noticed vomiting and two bloody stools after the prescription of a powder con- taining calomel, magnesia, and jalap. In the great majority of cases, however, the preparations of mercury do no harm whatever. Wachsmuth* thinks that mer- curial ointments make the swellings of the joints more obstinate : but no other observer has noticed the same mishap. Haemophilia influences very slightly, if at ali, the occurrence and progress of other diseases. The Ameri- can physicians enjoyed the advantage of observing families of these patients ; and they say that the diseases, to which they are subject, differ in no way in their course and character from those of other individ- uals. Like other children, they pass through measles, scarlet fever, and whooping cough, without anything remarkable ; and later in life, should they chance to suffer from acute disease, there is nothing characteristic either in the course or mode of recovery. They seem, however, rather more liable to acute affections within the chest, such as pneumonia and pleurisy, than to any other form of acute disease. And in some of these cases, there is a tendency, during the course of the disease, » Burnes, Lancet, 1840, Dee. p. 3 Elsàsser, Hufeland's Journal^ 405. Bd. Iviii. Stiick ii. p. 103. « Bicking, op. cit. p. 1 12. * Wachsmuth, op, ctt, p. 29. IDIOSYNCRACIES OF HJEMOPHILIA. 75 to haemorrhages, whether from the nose, which is the Chap. V. more common, ór from the urinary organs. Catarrhs, influenza, croup, rheumatism, peritonitis, orchitis and erysipelas have been observed amongthem, each running its usuai course. Among chronic diseases, rheumatism and ' scrofula' are mentioned most frequently. VieH, in his great experience of the large famihes at Tenna, says that, after haemorrhage, dropsy and gangrene are the most common causes of death.^ Gangrene is not an uncom- mon accident among the subjects of haemophilia ; Vieli says it is an ordinary result of a wound,^ and twelve other writers speak of sloughing or gangrene foUowing a traumatic haemorrhage, or an injury. Chronic skin diseases are seen amongst bleeders : chiefly forms of impetigo and * pityriasis.' Phthisis does occur amongst these patients and their families, but there is no apparent disposition to the disease. Convulsions are common when the loss of blood has been very great ; but epilepsy has only been noticed 4 times : in one case, a haemorrhagic cavity was found in the brain after death,^ In another, con- * Vieli, reportedbyGrandidier, must be great risk ofanextra- op, cit, p. 19. vasation of blood within the * Vieli, reported by Grandi- cranium at each epileptic at- dier, op, cit. p. 18. tack : practically this does not 3 In the case recorded by seem tò exist ; and there is also Cousins. (Med, Times and Gazeiie, no record of ecchymoses in the 1869, voi. ii. p. 278) The other face being noticed after the three cases are Gintrac's, where seizure, an accident not uncom- no post mortem examination was mon in some epileptics. Otte, allowed; Beier's, and Otte's, indeed, noticed that, during the where the boys were stili alive fit, ecchymoses did not follow at the time of publication. There bruìses. 76 IDIOSFNCRASIES OF HJEMOPHILIA. Chap. V. vulsions seem to bave preceded and attended the bleedings.' True gout is extremely rare amongst the subjects of haemophilia, as may readily enougb be supposed from the age of the majority of the patients. Those cases which are called gout by the Germans are nothing more thanthe peculiar joint swelling. In four of Rieken's patients there was a foetid dis- charge from the ear : in one óf them it almost disap- peared after the use of cod liver oil.* ^ Beier, De Haemophilia^ Diss. * Rieken, Neue Untersuchungen Inaug-. Berol., 1864, p. 27, «.j.w., passim. CHAPTER VI. MoRblD AnATOMY and PaTHOLOGY OF HìEMOPHILIA. The examination after death of persons who haveCnAP. VI. suffered from haemophilia has hitherto thrown but little ' light upon the disease. The number of such examina- tions is now very considerable ; but careful and thorough examinations are stili wanted. In the greater number of cases, it is stated that ali the organs examined, espe- cially the heart and vessels, were naturai. The appear- ances of death after great loss of blood are present ; the body is found emptied of blood, the skin and tissues extremely pale, the face and ears are semi-transparent, as if made of wax. The ecchymoses, if present during life, remain after death ; they may be noticed in the mucous membranes and connective tissue. The rigor mortis is often so considerable that the body may seem to bave gained several inches in length. Putridity quickly comes on. Such is the negative result of careful examinations made by Grandidier in three cases' ' Grandidier, op, cit, pp. 30 and old upon whomritual circumcision 151; and Schmidt's yb^r^^. Bd. had been dona : the third was a xxvìii. p. 170. The first-mentioned boy in his third year; nothing case was a boy of 1 3, whose unnatural was found beyond very pharynx was found to be changed thin coats to the stomach and in- into a red semi-fluid mass : the testines. second was a child a few days 78 MORBID ANATO MY OF HJEMOPHILIA. Chap. vi. and by Lebert,^ Elsàsser,* Moxon,^ Spahn,^ Assmann,^ and Resal,^ in one case each. In a bleeder, aged 12, at whose examination after death I was present a few years ago, nothing was found but great bloodlessness of every part. But although the bodies of bleeders show no Constant anatomical change, yet certain alterations bave been noticed with some degree of frequency : these are mostly an unusual thinness, or other disease, of the coats of the vessels ; or some mal-formation of the heart. Under these two heads, nearly ali the morbid appear- ances yet found may be classed. Blagden was the first to notice an unusual thinness of the arteries. In a young man, aged 27, the coats of the temporal artery and some other branches of external corotid were nearly transparent ; and they were thinner than usuai. The texture of the carotid, whichhad been ligatured, was naturai, but '*there were several opaque white depositions on the outer surface of its inner coat, such as precede ossification.'*^ But two years after, in 1819, James Wilson gave the foUowing account of the ^ Lebert, Arch, gén, de méd, 1837, sept. p. 40. No thrombus had formed above or below the ligatured points of Jthe radiai and brachial arteries ; but the man seems to have died on the same day that the arteries were tied. ^ Elsàsser, Hufeland's Journal, Bd. lix. Stuck iii. p. III. ^ Moxon, reported by Durham, Guy's Hospital Reports, 1868, voi. xiii. p. 491. ^ Spahn, Schmidt's Jàhrhh. Bd. cxxxix. p. 173. Small ecchymoses were found in the stomach. 5 Assmann, Die Hàmophilie, Diss . Inaug. Berol. 1869. p. 19. Both pleurae were full of fluid. ^ Resal, Quelques pages sur r he- mophylie, Thèse de Paris, 1861, p. 26. 7 Blagden, Med, Chir, Trans. 18 17, voi. viii. p. 227. MORBID ANATOMY OF HJEMOPHILIA. 79 examination after death of a boy, between 3 and 4 years Chap. VI. old, the subject of haemophilia, and who bled to death after biting his tongue. ** The whole of the viscera appeared to be perfectly healthy, but the aorta and every branch sent off from it seemed to resemble veins more than arteries ; the coats were not more than one half of their usuai thickness, they had not sufficient elasticity to preserve their cylindrical form in the dead body when deprived of blood ; and even in the popliteal artery, notwithstanding there had been so much loss of blood, the artery did not appear to be contracted, nor were any muscular fibres to be discovered in its coats."' Hooper also found, in a bleeder 25 years old who injured his arm by a fall from his borse and bled to death therefrom, '* numerous pellucid patches ali over the artery (brachial) through which the probe could be seen, and the profunda superior and inferior and ramus anastomoticus presented similar appearances. There was an evident deficiency ofthefibrous coat."* No further examination is re- ported. Fischer also found the walls of the arteries very thin, and their elastic coat transparent, in a bleeder aged 18, who died of the haemorrhage following the extraction of the stump of a tooth.^ In a case recorded by Lemp, the post mortem examin- ation was made by Professor Virchow ; there was found some fatty degeneration of the fibres of the heart ; and of ^ the inner coat of the aorta, an appearance not very rare at the age of 24. The aorta was narrow, and the thy- ' James Wilson, Lectures on the ^ Fischer, ^SìX^wSiòS^^Jahrhùcher, BloodyCtCy London, 18 19, p. 412. Bd. Ixxxvii. p. 136. * Hooper, reported by Burnes, Lanceiy 1840, Dee. p. 405. - 8o MORBID ANA TOMY OF HJEMOPHILIA. Chap. vi. mus persistent. No alteration could be detected in the small arteries or capillaries ; nor in the nerves,' ^ Lemp, De haemophilia nonnulla, Diss. Inaug. Berol. 1857, p. 17. Since, to use the words of thìs author, "hucusque sectio tanta diligentia et a tanto antistite non ' instituta/' it may be desirable to g-ive the chief part of the report of this examination, especially since the dissertation is rather difficult to procure. "Vena cruralis omnibus locis amplissima, valvulae evidentes, verum tenues, tunica intima spis- sata, partim maculis conspersa. Arteriae prò ratione angnstae, parietes satis spissi, elasticitas potissimum in diametro longitu- dinali permagna, tunica intima omnino sana, paucis Iqcis nubila, obscura et albida. ''In cavo abdominis praeter parvam copiam transsudati cada- erosi nusquam adhaesio aut pig- mentatio quaedam inventa est . . In abdominis visceribus nulla mutatio notabilis detecta. , ... In mediastino antico gianduia thymus perstitit Pulmones parum hypostasi oppleti, ceterum sani. In sacco pleurae et pericardio exigua transudati cadaverosi co- pia. Cor nonnihil parvum, pal- lidum, in basi et ventriculo dextro satis large adiposum, in parte anteriore et posteriore, inprimis dextra maculae tendineae perspi- cuae. Valvulae arteriarum bene coierunt, in utroque ventriculo tenues et satis fenestratae fuerunt . . . . foramen ovale perfecteclausum . . . Caro musculosa ubivis coloris pallidi, subflavi. . . Aorta, ubi valvulae connivent, cum maculis diversis, aliquantum elatis, adi- pose degeneratis. Circuitus in- terior vasis hoc loco 5*6 centm., dum circuitus arteriae pulmonaris, ubi valvulse connivent, 6*7 centm. Aorta toto in tractu angusta, tenuis et specie quasi magis infantili, ceterum valde elastica. . . Tunica intima aortae ascendentis et caro- tidum ferme normalis. In regione ligamenti arteriarum aorta ad circuitum interiorem 4*5 centm. per logum cymatii instar promi- nentem coangustata est. Ab hoc loco usque ad bifurcationem com- mutatis quaedam singularis ob- servari poterat, modo magis ad parietem posteriorem, modo ad anteriorem pertinens. Cemeba- tur in elevationibus quibusdam undulatis et Inter se conjunctis tunicae intimae, quae saepissime ovatae ad glandularum Peyeri ordinem in acervos constructae videbantur. In circuitu quoque ramorum, praesertim deorsum deflectentium concretiones parvae MORBID ANATOMY OF HJEMOPHILIA. 8i Schiinemann gives the history of a lad, aged 21, who Chap. VI. bled to death after the removal of a molar tooth ; the post mortem appearances recali those of the foregoing case ; there was fatty degeneration of the fibres of a heart, somewhat enlarged ; the liver also enlarged and fatty ; together with a general want of blood throughout the body. But besides this there was an unnatural condition of the vessels : their walls were in some places unusually thin, flaccid, and transparent.' Changes in the heart bave been rather more frequently observed. A writer in 1818, commenting on the ex- amination of a bleeder recorded by the two brothers Buel, says that ** we bave witnessed the examination of the body of a young man who died from nasal haemor- rhage, and who was represented to bave been subject to bleeding to a great extent from the slightest causes, atque in ostiis arteriarum lum- balìum infimarum maculae mag*- nae scleroticae exstabant. " Elevatìones, quas eommemo- ravimus, undulatae jam ad tuni- cammediam pertinent, quae exhìs albide obnubilatur ; tunica intima autem, fibrislongitudinalibuscon- texta, accurate perspecta strias maculasque subflave albas osten- debat per degenerationen adi- posam exortas. Maculae hujus generis singulae partem convexam arcus aortae obsidebant. "Cum in corde, tum in vasis majoribus copia mediocris san- guinis bene concreta inventa est. . • "Exploratio microscopica cor deg-eneratione adiposa modice correptum, arteriarum tunicam intimam multis locis valde correp- tam ostendit ; nihil taraen pate- fecit, quod ad arteriarum minorum et capillarium mutationes perti- neret. In illis elementa adeo muscularia facillime et largiter sejungi poterant atque in arteriis tantummodo minoribus femoris passim inter fibras elasticasguttae dispersaeadipis exstabant. Neque in nervis quidquam a norma discrepans detectum." ^ Schiinemann, Arch, f, path. Anat, Bd. xli. p. 289. M 82 MORBID ANATOMY OF HjEMOPHILIA. Chap. vi. in which the heart was found to be of four or five times the usuai size, but without any marks of disease. The extraordinary bulk of that organ arose from a pre- ternatural development of its muscular structure."' Schneider found in the body of a lad, aged 17, who belonged to a bleeder family, and who died of bleeding from the nose, both pleurae and the pericardium un- naturally fiUed with a quantity of serous fluid, the heart enormously enlarged,* containing no blood, the wall of the right ventricle remarkably delicate, and thin like membrane, the wall of the left ventricle unnaturally tough and thick ; the valves and chordae tendineae like cartilage, and in some places almost as hard as bone ; the coronary veins full of blood.^ In the case already mentioned of a young student who bled to death after a mere scratch received in a duel, Escherich found ali the organs naturai ; the heart very pale, and, saving a small coagulum in the right auricle, containing no blood ; the foramen ovale partly open, and the septum of the auricles very thin and transparent with an open- ing nearly round and about 6" in diameter. Upon the side of the right ventricle there was a tendinous cord, scarcely 1'" thick or .5" long stretching to the opposite edge, and passing from back to front over the opening.* This must bave assisted to dose the opening in the septum of the auricles, and to diminish the evil eff"ects, ^ London Medicai and Physical 3 p. J. Schneider, (of Offen- Joumal, 181 8, voi. xl. p. 431. burg") SchxaìàMs Jahrbb, Bd. xxiv. This is the case referred to by p. 356. Nasse. (Horn's ArchiVy 1820, Mai- "♦ Escherich, quoted by Schnei- Juni, p. 428.;. der, loc. di, 2 " ungeheuer gross" MORBID ANATO MF OF HJEMOPHILIA. 83 if any, of such a communication. A similar thinness Chap. VI. of the septum of the auricles was found by Schliemann ^ in a Jew bleeder aged 15 ; a part of the septum of the ventricles of this boy was also deficient in muscular fibres and only closed by a thin transparent membrane ; the pulmonary artery was unusually narrow and as thin as a vein.' Gavoy also found in a boy, aged 14, the sub- ject of haemophiHa, and who died in the hospital at Strassburg, hypertrophy of the heart and thinness of the walls of the pulmonary artery.* Besserer noticed in a boy aged 6, who is said to bave died of * arachnitis/ that the left heart was hypertrophied, and contained much white and firm fibrinous coagula.^ In one of Grandi- dier's cases, the only morbid appearance was a thinness of the right heart/ Schònlein seems to bave thought the round and foetus-like appearance of the heart to be Constant in this disease, and to denote its connexion with cyanosis.5 Especial weight was laid upon the im- perfect development of the heart, the patency of the foramen ovale, and the deficiency of the muscular fibres in the walls. Mutzenbecher examined the body of a boy who died from the bleeding into the connective tissue after a fall upon the chest. The whole of the intermuscular and subcutaneous tissue was full of dark coagulated blood. ' Schliemann, quoted by Gran- 3 Besserer, Canstatt's Jahres- didier, op, cu, p. 85. herìcht f, 1845, B^« "• P« 29. * Gavoy, Canstatt's Jahresher- * Grandidier, op,cit,^, 31. icht fùr 1862, Bd. ìv. p. 155. ^ Schònlein, Vorlesungen ueber Abstract of L Hèmophtlùy Thèse Path,u, Ther, 3tteAuflage, 1837, de Strasbourg, 1861. Bd. ii. p. 63. 84 MORBID ANATOMY OF HjEMOPHILIA. Chap. vi. There were also some extravasati ons of blood in the 'lungs.' There are two cases shortly mentioned by Mr. Lane,* as occurring in the practice of Dr. Wilson, where death was caused by extravasation of blood within the cran- ium, as a consequence of blows on the head. Very similar to these two cases is the account given by Dr. Cousins of a lad of i6 who fell forwards in an epileptic fit, struck the forehead on the floor, and died. At a post mortem examination made 48 hours after death, an ecchymosis was noticed on the fore- head and ** a moderate amount of effused blood was found under the pericranium, corresponding in situa- tion to the external injury. On removing the skull and dura mater, a thin layer of blood appeared covering the anterior two-thirds of the left hemisphere. The brain was congested throughout, and a considerable extravasation was also found at the base and upper part of the spinai cord. On section, a cavity was dis- covered in the anterior lobe of the left hemisphere about the size of a small walnut. Its walls were irregu- lar, and of a light brownish colour. The cavity was empty, and it did not encroach anywhere upon the surrounding grey matter.''^ The lungs and heart are said to bave been healthy. ^ Mutzenbecher, quoted by 3 Cousins, Medicai Times and Grandidier, op, cit. p. 85. Gazeiie, 1869, voi. ii. p. 278. * Lane, Lancet, 1840, Oct. p. The epileptic attacks dated from 187. These cases belonged to a fall on the left forehead 7 the same family as those describ- months before death : memory ed by Mr. Wilson in his Lectures and mental power were much on the Blood^ &c. impaired. MORBID ANATOMY OF H/EMOPHILIA. 85 In a case recorded by Liedbeck of Stockholm, a lad Chap. VI. of 16, the subject of haemophilia, received a blow upon the right tempie ; the tempora! muscle became infil- trated with blood, and death foUowed. The examina- tion after death showed that there was an extravasation of blood between the membranes at the base of the brain : this blood was coagulated, but that in the heart was not. AH the other organs were found naturai ; but the vessels were not examined : this was also the case in this patient's brother, who died, at the age of ig, of haemorrhage foUowing the extraction of a tooth.^ Dr. Buss has recorded a case in which haemophilia was associated with a misplaced spleen. The patient, a young man, aged 21, was seized with symptoms of peritonitis six days before death. On opening the abdomen, 24 hours after death, the intestines were found surrounded by a large quantity of grumous blood. Beyond great pallor, nothing amiss was noticed with the liver, kidneys, pancreas, and intestinal tract. On searching for the spleen, it was found resting on the internai iliacus muscle in the left iliac fossa ; it was doublé the naturai size, soft, and ruptured at its in- ternai border. The thoracic viscera were somewhat pale and flabby.* That much light should be thrown upon the patho- logy of a disease like haemophilia by coarse anatomica! examination was not, perhaps, to be expected. The malformation of the heart, which seems more frequently ^ Bjòrkman and Liedbeck, « Buss, Medicài Times and Gaz- quoted by Huss, Archives gèn, ette^ 1868, voi. ii. p. 530. de Méd.y 1857, voi. ii. p. 178. 86 MORBID ANATO MY OF HJEMOPHILIA. Chap. vi. than any other tangible lesion to accompany haemo- philia, may perhaps be looked upon as another expres- sion of the imperfect development of the whole vascular system. The observations on the greatly diminished thickness of the arteries are important ; and it is to be regretted that three of these cases were examined before the microscope was brought into such general use as at present, and thus valuable opportunities of widening our knowledge were lost. In Lemp's case, however, Vir- chow could find no alteration of the small arteries or capillaries : nor could Morel in Gavoy's.^ Should any opportunity hereafter occur to examine the capillaries after death, it would be best to take those parts which were most subject to bleedings during life ; for example, the mucous membrane of the nose, when the patient had died of epistaxis. The microscopical observation is, it must be confessed, full of difficulty, and requires very many concurrent favourable circumstances ; but no opportunity for making it should be lost. It is unfortunate that the lower animals should be quite free from haemophilia :* they would otherwise have afforded very valuable materials for the most in- ^ As quoted by de Fleury, Mém, de la Soc, méd,-chir. de Bor- deaux y 1866, t. i. p. 305. * The case described by Schutt (Schmidt's yahrbucher, Bd. cxxiiì. p. 117) of a haemorrhage from the skin and other parts, in a borse, seems to belong rather to purpura, or some allied affec- tion, than to haemophilia: and the case which Mélon (Vir- chow's J ahreshericht /. 1868, Bd. i. p. 520.) has describ- ed under the name of haemophi- lia in the borse does not, from the description, appear even to belong- to the class of hsemor- rhagic diathesis. PA THOLOGY OF HjEMOPHILIA. 87 structive observations upon the aetiology and pathology Chap. VI. of the disease. The pathology of haemophilia is stili buried in the deepest obscurity : nor are any glimmerings of light to be discovered in the numerous theories which bave been advanced as to the nature of the disease. Some writers regard haemophilia as an anomalous form of other diseases ; or as dependent upon some alteration in the blood, or in the blood and blood vessels together, or as a disease of the whole vascular system ; or a disease of the capillaries only. These various theories will now be considered more at length. Consbruch," Elsàsser,^ and Krimer^ ali mention the * gout' in their reports, either the patients themselves or their relatives being subject thereto. Nasse men- tions this with approvai : he says that gout is both hereditary, and far more frequently seen in men than women ; that the vascular system in gout often suffers, as the tendency to bleedings and haemorrhoids testify.* Rieken regarded haemophilia as an anomalous variety of gout and grounded this assertion upon the four fol- lowing propositions : ** I. The tendency to extreme haemorrhages has been of late observed only in those persons whose parents or grandparents bave suffered from gout. ** 2. In those members of bleeder families who bave escaped the tendency to haemorrhage, gouty paroxysms may often be observed. ^ Consbruch, Hufeland's Jour- 3 Krimer, Horn's ArchtVy 1820, nal, Bd. xxx. Stuck v. p. 117. Mai-Juni, p. 413. * Elsàsser, ibid, Bd. Iviii. Stuck ^ Nasse, ibid, p. 429. ii. p. 97. 88 PATHOLOGY OF HjEMOPHILIA. Chap. vi. **3. In bleeders themselves, gouty paroxysms are nearly always seen, and sometimes an alternation of the joint affection with the bleeding. '*4. Gout is a disease which stands in a very dose relation to the blood and blood vessels, and often ap- pears to be a direct cause of haemorrhage.'*' Unfortunately, none of these propositions can now be maintained. As to the first and second, haemo- phiHa is by no means so exclusively seen in gouty famiHes : gout does occur in a certain number of bleed- er famiHes, but haemophilia commonly occurs without any mention of gout being detected in the family history. Then as to the third proposition, the swelHng of the joints peculiar to haemophilia has been mistaken for true gout, a mistake not uncommon among the earlier writers on haemophilia. The fourth proposition may, however, find defenders at the present day. I am aware that a very general impression exists that gout favours the occurrence of haemorrhoids and bleedings. But out of 50 of my patients at Saint Bartholomew's Hospital, who sufFer from well-marked gout, of dura- tion rarely less than io years, I bave found on careful inquiry that not more than 3 bave at any time in their life been subject to haemorrhoids, and none subject to bleedings from other parts. These observations bave led me to suspect very greatly the statement that bleed- ings are common in gout, and this is a point which . ought clearly to be made out, before a theory of haemo- philia be built upon it. * Rieken, Neue Untersuchungen in Betreff der erhlìchen Neigung zu tddtlichen Blutungeriy Frankfurt a.M. 1829, p. 87, et seqq. PATHOLOGY OF HJEMOPHILIA. 89 Schliemann looked upon hsemophilia as a disease in- Chap. VI. termediate between cyanosis and scrofula ;' and Hey- felder, as intermediate between gout and scrofula.* The meaning of the word scrofula is so undetermined that it is not worth the time to stay to discuss such opinions. S. G. Vogel thought that a scorbutic state of the blood might occasionally He at the bottom of the phae- nomena ; but this opinion seems intended by him to be applied to only one case, that of Rave's; which Grandi- dier regards as intermediate between scurvy and true hamophilia.3 A relation to cyanosis was thought of early in the history of haemophilia. Nasse in 181 1 drew a distinc- tion between the blood in cyanosis and the blood in hsemophilia ;* and J. F. Meckel, commenting on the American cases, says that cyanosis is plainly only a higher grade of haemophilia.^ Later on, Nasse com- pared the two diseases ; both present bleedings difficult to check ; both affect the male sex ; both show a great mortality early in life ; in both there happens occasion- ally a general blueness of the body ; and in both, also, the patients are exceedingly passionate.^ But Schon- lein was the most active supporter of the theory of the connection of cyanosis with haemophilia ; he appears to ' Schliemann, De disposiHone ad Neue Ausgabe, Theil v. p. 14. haemorrhagias pemiciosas haeredi- 4 Nasse, Reil's Archiv f, d, tarìa^ Diss. Inaug. Wirceb. 1831, Phys, 181 1, Bd. x. p. 266, Note, p. 45 . 5 J. F. Meckel, Deutsches Archiv * Heyfelder, Medizin, Zeiiung /, d, Phys, 18 16, Bd. ii. p. 140. (Veretns), 1833, p. 216. ^ Nasse, Horn's Archiv^ 1820, 3 S. G. Vog-el, Handb. d. proci, Mai-Juni, p. 429. Arzneywissenschafty Stendal, 1820, N 90 FA THOLOGY OF HJEMOPHILIA. Chap. vi. have made many post mortem examinations in which a round and foetal shape of the heart was observed ; as as well as a deficiency in the muscular walls, a mem- branous septum only being present, and the foramen ovale patent.' In his nosology, the disease is placed between cyanosis and chlorosis. Schònlein doubtless laid too much stress upon the malformation of the heart, yet he did good service by drawing atten- tion to the ill-developed condition of this organ in some cases, a point which will be hereafter more dwelt upon. The theory of some alteration in the blood is a favour- ite explanation of the phaenomena of haemophilia. In i8i i, Nasse sought to explain the unnatural fluidity of the blood, to which he attributed the disease, by a hyper- oxydation ;* but in 1820, he attributed this unnatural fluidity to a fault of development, the blood remaining in a lower stage of growth.^ The same opinion had been expressed by Meckel with the addition of a com- parison of the blood in haemophilia to that of the Ceta- cea/ The belief in the extreme fluidity of the blood depended upon the older observations, now known to be incorrect, of the absence of coagulation : and this cir- cumstance, joined to an assumption of an alteration in the blood vessels as well, was the most common theory of the disease for many years, Rokitansky having lent the weight of his authority to the statement that in haemophilia there was a thin watery condition of the * Schònlein, loc, cit, didier says that Nasse wìthdrew * Nasse, op, ctt, p. 267, Note. this opinion in 1843. 3 Nasse, op. di, p. 431. Gran- ^ J. F. Meckel, op. cu. p. 138. PATHOLOGY OF HjEMOPHILIA. 91 blood, joined to a great delicacy of the vessels, and Chap. VI. liability of these to injury.' The theory of an increas- ed fluidity of the blood has of late been revived by Gavoy. He believes that there is something in the blood which renders it more fluid, an alkaline salt for instance.* His analyses, however, do not show a larger percentage of salts than is usuai in health.3 The theory of an alterati on of the blood, especially if this alteration be attributed to an increase in the amount of alkaline salts, has gained some support from the observations of Prussak. He injected a 2 per cent, solution of chloride of sodium into the lymph sacks of frogs, and found that the red corpuscles everywhere began to escape through the uninjured walls of the vessels, and to be visible in the tissues around. Chlor- ide of sodium was also daily injected into the con- nective tissue of a rabbit, and after death, numerous ecchymoses were found in ali the organs.* The hypothesis of a change in the blood may be * Rokitansky, Handh, d, allg, path. Anat,y Wien, 1846, BA i. p. 167. It is only just to mention that this passage does not ap- pear in the third editìon of this work. * Gavoy, quoted by de Fleury, Mém, de la Soc, méd.-Mr de Bor- deaux, 1866, t. ì. p. 307. 3 For the analyses, see p. 61. ^ Prussak, Sitzungsb. der math^ em.'naiurwùsen. Classe der kazserL Akad, der Wùsensch,, Wien, 1867, Bd. Ivi. Abth. li. p. 13. I haye several times repeated these ex- periments on the frog" with suc- cess ; but I have not been able to produce these minute haemor- rhages by the ìnjection of any other halogenous salt, paying especiai attention to the action of the iodide and bromide of potas- sium, after the use of which Ricord and Walshe are said to have noticed a disposition to hae- morrhage. 92 PATHOLOGY OF HjEMOPHILIA. Chap. vi. serviceable in the explanation of a temporary haemor- rhagic diathesis ; but I doubt very much if such an alteration be the source^ of a congenital disease, lasting, like hsemophilia, throughout life. Besides, there is not one recent observation of any deviation in the blood from the standard of health. I do not say that such will not be found : but there is at pre- sent no evidence of such alteration. In any future analyses of the blood in haemophilia, it will be necessary to make exact observations on the amount of salts present. Especial attention should be paid to the amount of chloride of sodium. Unfortu- nately, the method of estimation which is used by the chemists for any one salt is stili very defective, being in fact little more than a guess ; so that until the process for estimating a salt separately shall bave been per- fected, Chemistry cannot be relied upon with much confidence to give assistance in this direction. It would always be well, however, to ascertain the gross amount of salts contained in the blood ; and, if possi- ble, the amount contained in the plasma and corpuscles respectively. The theories which refer the phsenomena of this dis- ease to some alteration in the vessels will next be con- sidered. Autenrieth and Wedemeyer think that there is a paralytic condition of the capillaries, brought about by their imperfect development.' Meinel also is of ' Autenrieth and Wedemey- does not mention haemophilia ; er, quoted by Wachsmuth, op. only scuny and the Morbus ma- cit. p. 42. Wedemeyer {Unterà culosus Werlhofii are spoken of suchtmgen ueher dm Kreislauf des as explicable by a theory allied BlutSj Hannover, 1828, p. 327) to that given in the text. PATHOLOGY OF HJEMOPHILIA. 93 Opinion that there is a congenital imperfect vitality of Chap. VI. the capillaries from which they are unable to resist the flux of blood tp any part, and thus an escape of blood takes place with or without a rupture of the walls.' Wachsmuth assumes a congenital disproportion be- tween the increased vitality of the blood and the power of resistance possessed by the capillaries which are too delicately organized, and sometimes wanting in tone.* AH depends, in this theory, upon the meaning of the word vitality: Wachsmuth seems to think that it is allied to something which was called hyperoxydation by Nasse. I must, however, confess my inability to understand what is meant. But Resal has adopted it, giving this definition to the word vi- tality: an increased power of making blood. This increased power of making blood, whether congeni- tal, hereditary, or acquired, causes a reaction in the organism, and thus haemorrhages occur at those parts of the capillaries which are weakest or suffer from atony.3 ResaPs hypothesis rests upon the assump- tion that there exists in haemophilia a power of quickly renewing the blood, when much has been lost by bleed- ing. Some few observers bave noticed this in their patients, but it is far from being a universal law in hae- mophilia. After a great haemorrhage, these persons sufFer from anaemia for many months ; the power of rapid convalescence is not a feature of the dis- ease. There is yet another theory of a disturbed innerva- * Meinel, quoted by Grandi- * Wachsmuth, op. cu, p, 43. dier, op. cit, p. 114. 3 Resal, op, cit. p. 75. 94 PATHOLOGY OF H^MOPHILIA. Chap. vi. tion of the capillaries. Cochrane attributes the hasmor- rhages to the absence of nervous influence in the seat of the disease and consequent decreased vital action. '* Owingto this decrease of nervous power, the unresist- ing vessels in the congested part become enlarged ; and those of them which admitted only the transparent and more fluid portion of the blood, now admit the red globules, distending their calibre, and destroying their tonicity : hence haemorrhages, &c.'" Tamme Beth was inclined to believe in the nervous character of the disease, and spoke of the striking value pf animai magnetism.* Martin attributed the symp- toms to some nervous influence : ali the bleeders known to him were unable to indulge in mental or bodily exer- cise without fear of bleeding; and mental emotions, terror, fear, such as might be caused by scoldings ^nd small punishments, of a certainty produced hae- morrhages.3 Reinert agrees with this, and believes further in some alteration of the vaso-motor nervous system, an enfeebling of the sympathetic which allows the vessels to dilate even to bursting/ Otte was led to entertain the hypothesis of an altera- tion in the nervous system by observing the temporary disappearance of the Kamorrhagic diathesis in some bleeders. He noticed especially in bis own patient, who suffered from epileptic attacks, that although the boy was accustomed during the convulsions to strike him- self violently against surrounding objects, yet no ecchy- ' Cochrane, Z<»^^/, 1842, Aprii, 3 Martin, quoted by Reinert, p. 149. Ueher Haemophilie, Diss. Inaug". «Tamme Beth, quoted by Gòttingen, 1869, p. 23. Grandidier, op, cit. p. 1 14. 4 Reinert, loc, ctt. PATHOLOGY OF HjEMOP BILIA. 95 moses were produced. Was this due to some nervous Chap. VI. influence upon the vessels during the paroxysm ? The nervous alteration causing the haemorrhages may re- semble that exercised on the vessels of the neck and ear of the rabbit when the sympathetic in the neck is divided. So in haemophilia, one or two nerve tracts only may be affected at one time, and the various pheenomena may be caused by occasionai alteration in the degrees of tension in the vessels, while the place, where this alteration of tension occurs, varies. The difficulty of arresting the haemorrhage may be explained on the same theory : the blood continues to flow until the nervous influence causing the congestion and stasis has ceased to act, thus allowing the walls of the vessels again to recover their normal tone, so that an opportunity is given for the formation of a thrombus ; or, in the case in which the blood is poured out into the tissues, the blood may coagulate around the vessels, and by its pressure, cause a cessation of the haemorrhage, before this point of normal tone is reached. He closes his argument by some remarks on the cases in which a haemorrhagic diathesis has been set up after great mental emotion.' The theories of Martin, Reinert, and Otte are identi- cal in principle, and may be discussed together ; they ali make the essence of haemophilia to He in some alteration of the functions of the vaso-motor nervous system. Martin seems to base his theory on the as- sumption that mental emotion produces bleeding in haemophilia with great ease. Now as a matter of fact, ' Otte, Ueberdie Bluterkrankheit, Leipzig, 1865, p. 41, ^/ seq. 96 PATHOLOGY OF H^MOPHILIA. Chap. vi. mental emotion is not mentioned by the great majority of observers as an exciting cause of heemorrhage ; there are only three writers who speak of it ; and there- fore any theory based upon this must fall, unless a far greater number of cases be brought together. As to the influence of the vaso-motor nervous system : it may be well discussed, whether the present state of knowledge warrants the belief in the power of the ner- vous system to produce haemorrhage. When the sym- pathetic is divided in the neck of rabbits great hyperaemia ensues, but no haemorrhage, although Bouchard has succeeded in producing ecchymoses in the paralysed ear by raising the blood pressure.' The experiments of Pincus,* and of Moritz Schiff^ show only that deep alterations of nutrition, hyperaemia and sloughing, not simple haemorrhages, foUow the injury of vaso-motor nerves or of the meduUa oblongata. Indeed the latter observer found that no haemorrhages followed the re- moval of the nerves of the stomach.* The observations of Brown-Séquard upon the haemorrhages in remote or- « Ch. Bouchard, De la Paiho- ghne des Hèmorrhagtes, Paris, 1869, p. 80. The superior cer- vical ganglion was removed from the left side of a rabbit, and the aorta tied below the renals. Small haemorrhagic points were soon after observed in the paralysed ear. But in two other experiments (p. 121) he failed, even after ligature of both jugiilars, to produce ecchy- moses. 2 Pincus, quoted by Samuel, Die trophischen Nerven, Leipzig, 1860, p. 45. 3 M. SchifF, lezioni di fisiologia sperimentale, Firenze, 1866, Lez. xxix. p. 289 et seq. ; Lez. xxxix. p. 393 et seq. 4 M. SchifF, Leqons sur la Phy^ siólogie de la Digestione Florence, 1867, Lecture xxxv. PATHOLOGY OF H^MOPHILIA. 97 gans which follow injury of the nervous centres are Chap. VL important :' but it is quite possible that the explanation of these haemorrhages mayfall outside the nervous system. Thus at the present moment there seems scarcely enough evidence to allow us to assume the fact that haemorrhages may he caused by the action of the vaso-motor system only, although, at the same time, such an assumption is highly probable ; and the vaso-motor nerves may here- after be found to bave a great share in the pathology of haemophiHa. The theory of innervation is almost the only one which offers any explanation of the phae- nomenon of the disappearance and aggravation of the haemorrhagic diathesis at varying times, It is necessary just to mention the view which Gran- didier has propounded with reference to haemophiHa. It is a union of two preceding theories : both the blood and capillaries are at fault ; the blood is wanting in fibrin, and there is an imperfect action in the atonie capillaries, the walls of which are thin and readily torn. He seems also to think that there is a want of con- tractile power in these latter, which helps to keep up a haemorrhage once established.* Nearly 20 years ago, Virchow drew attention to the important part which the spleen plays in ali haemor* rhagic diatheses.^ Of the truth of the connexion be- tween the organ and the constitutional state, no one can doubt, after so exquisite an example as that which occurs in leucaemia : but I am scarcely inclined to think that these remarks of Professor Virchow were ^ Brown-Séquard, Z^«^^/, 1871, 3 Virchow, Handb, der spec, voi. i. p. 6. Path, u. Ther., Erlangen, 1854, 2 Grandidier, op, cit, p. 115. Bd. i. p. 247. O 98 PATHOLOGY OF HJEMOPHILIA. Chap. vi. intended by him to apply to haemophilia ; they seem rather intended to refer to the temporary haemorrhagic diatheses which occur in the course of so many dis- eases, than to be any attempt at the explanation of a congenital permanent disease like haemophilia. Of greater interest is his commentary upon Lemp's case, already mentioned.' The whole of the appearances in this case recali those seen in chlorosis. In chlorosis, the development of the heart and aorta is very back- ward ; later, however, foUow enlargements of the heart. Bleedings are common and violent in chlorosis, and they might bave some relation to the alterations in the arterial walls : the round ulcer of the stomach always corresponds to the track supplied by certain arteries. There is much in favour of the congenital or early development of the predisposition to chlorosis. Have the narrowness and great elasticity of the arteries any- thing to do with haemophilia ? They may increase the blood pressure in the arteries, thus producing the dis- position to bleed, and maintaining it when once established. The causes of a haemorrhagic diathesis must be sought in an arrest of the growth of the vessels,* and it should be noticed that, in Lemp's caso, the thymus was persistent.^ ' See p. 80. * " Hemmung der Gefassbil- dung.*' 3 Virchow, Canstatt's Jahres- hericht /, 1859, Bd. iv. p. 267. De Fleury {op, di. p. 309) has also made the comparìson be- tween chlorosis and haemophilia; but on quite different grounds from those of Professor Vir- chow, and also, it would appear, in ignorance of his views. The comparison seems based chiefly on the anaemia which sometimes exists in haemophilia, and also on the pica which has been noticed in some few cases. PATHOLOGY OF HJEMOPHILIA. 99 It is ìmpossible not to remark, in spealcing of this Chap. VI. comparison between haemophilia and chlorosis, with ali the deference that is due to any opinion of Pro- fessor Virchow, that bleedings are certainly not so common in the latter disease as might be supposed from the foregoing description. In fact, hamorrhage is, in my necessarily short experience of chlorosis, one of the symptoms which are the exception, and not the rule ;' and this circumstance appears to me to be the weakest part of the theory which has just been set forth. Of the Constant presence of a narrow aorta in chlorosis, it is unnecessary bere, nor perhaps does it become me, to speak. On reviewìng the present state of our knowledge of the pathogeny of haemorrhages, it would seem probable that, in nearly ali cases, an alteration of the vessels precedes the effusion of blood :* haemorrhages in chron- ic diseases, without previous disease of the blood ves- sels, are exceedingly rare. It is highly probable, then, that in haemophilia, a chronic disease, some change in the vessels is present. As yet, it is true, none has been discovered ; but the foUowing hypothesis has seemed to me capable of explaining some of the phae- nomena of h^mophilia, » I am aware that Trousseau has pointe4 put the fact that menprrhagia and epistaxi§ are 3ometime3 the consequences, and not the causes, of chlgrosis. But he does not regard these phaeno» mena as very common. Is it possible that chlorosis may con- vey in Germany a notion difFerent frpm that in England ? 2 Even in some acute hae-» mprrhagic diseztses, as purpura, disease of the blood vessels has been detected, (Wilson Fox, British and Foretgn Med.-chtr. RmeruOy 1865, Oct. p. 490.) loo PA THOLOGY OF HJEMOPHILIA, Chap. vi. In haemophilia there is an imperfect development of the whole vascular system. In many cases, the heart retains an appearance similar to that in the foetus, and in parts, the muscular fibres are wanting in the ventri- cular or auricular wall, being replaced by a membranous septum only. In others, the arteries are exceedingly thin, transparent, and unable to preserve a circular section. These appearances render it probable that there is an arrest of development, or backwardness of growth, in the heart and blood-vessels. Now true haemophiHa is a congenital disease, and it may be that the foetal state of the vascular system persists in extra-uterine life. Newly-formed vessels are very liable to haemorrhages, spontaneous and traumatic : the new- born infant bleeds much more readily, and for a longer time, than the adult. The vessels of newly-formed granulations, of rapidly growing tumours, bleed upon very slight provocation. If the vessels in haemophilia were permanently in the foetal or newly developed state, frequent and long-continued bleedings might well be expected from them. And in this case it would not be surprising that not much alteration should be detected with the microscope ; which has happened in the two cases' in which such examination was made. The occasionai disappearance of the haemorrhagic diathesis in cases where the patients bave reached a certain age, may be explained on this hypothesis. In most of the cases in which it has been recorded, the patients bave lost the disposition to haemorrhage between the 25th and 30th years of life, a time about which the ' Gavoy, loc, cu, Lemp, loc, cit* PATHOLOGY OF HJEMOPHILIA. loi human frame is said to become fully developed, and in Chap. VI. which development it is possible that the vascular system may share.^ It will he at once observed that this theory can offer no explanation of the occasionai temporary disappearance of the diathesis. It is, also, only the removal of the difficulty one step backwards. The progress of patho- logy will soon show whether it is, or is not, worthy of any further consideration. I am not acquainted with the record of any examìna- tion, after death, of the joints of a patient suffering from the swelling common in haemophilia.^ The nature of the swelling is as obscure as the rest of the pathology of this disease. Dubois long ago asserted that the fluid, so plainly contained within the capsule of the joint, was blood."* This statement was, however, everywhere received with great reserve, noproofhavingbeenbrought ^ Since these lines were writ- the fourth edition oì Die Cellulare ten, I fìnd that I have no less pathologù, Berlin, 187 1, p. 257. an authority than that of Pro- ^ Lemp, indeed, {De haemophi- fessor Virchow in support of this Uà nonnulla, p. 18) records the theory. Speaking of the delicacy examination of the knee long" of newly formed vessels and after ali inflammation had sub- their liability to bleed, he says : sided : In articulatione genu "■ So mòchten sich manche er- tota fere membrana synovialis ** bliche Formen hàmorrhagis- multo pigmento rubiginoso im- "cherDiatheseerklàren."(Zra«^i5. pietà et obtecta erat. Synovia d, spec. Path, «. Ther, Bd. i. p. vero valde imminuta, nec minus 240) . At present. Professor Vir- cartilagines paullum dissolutae chow does not seem to have any erant. theory to offer to explain the 3 Dubois, Gaz, méd, de Paris^ pathology of hsemophilia. See 1838, p. 43. 102 PATHOLOGY OF HJEMOPHILIA. Chap. Vl.forward by Dubois, until recent observations showed the possibility of an extravasation of blood within the joint being the cause of the swelling. In Reinert's case, the capsule of the shoulder-joint suppurated, whereupon a great quantity of blood escaped,' and, it is assumed by the author, escaped from the interior of the joint. Assmann, also, saw a considerable quantity of fluid blood escape upon puncture of the swoUen knee of a bleeder.* It is very unsafe, however, with Reinert, to infer that an effusion of blood into the joint precedes ali the articular swellings : it is doubtless an explanation of many cases ; but scarcely, I am inclined to believe, of ali. In the absence of ali knowledge of the morbid anatomyofthis state of the joints, it is best to remain silent until something certain be attained. ^ Reinert, Ueher Hamopkilie, * Assmann, Die Hàmophiliey Diss. Inaug. Gòttingen, 1869, p. Diss. Inaug. Berlin, 1869, p, 12. X2, CHAPTER VII. DiAGNOSIS AND PrOGNOSIS OF H^MOPHILIA. The diagnosis of haemophilia presents, in its prò- Chap. VII. nounced form, but little difficulty. It is otherwise, however, when an incomplete and low grade of the disease is seen, especially if the patient should then happen to be a woman. It is easy to make the dia- gnosis when a boy has suffered, since early infancy, from ali kinds of bleeding, especially traumatic, and the joints bave as well been repeatedly swollen. But in the second degree of the disease, when spon- taneous bleedings only bave been noticed, and no liability to traumatic baemorrhages exists, a great deal of caution has to be exercised ; for it is no uncommon thing for boys to suffer repeatedly, before puberty, from severe epistaxis.' Several points must be enquired into : the existence of haemophilia among the kinsmen will greatly ' " Narium haemorrhagia, uti "regulariter et sincerius competit "junioribus, pueris, et adoles- " eentibus, in sexu maxime virili ; ''Ita citra piane peculiares ra- " tiones, haereditariae disposi- "tionis, aut adsuetudinis, aut *' externarum commotionum in- *' solentiorum, non evenit etiam, " nisi manifestius plethoricis." Stahl, Theoria Medica Vera, Halae, 1708, p. 701. Stahl several times speaks of an hereditary disposi- tion to haemorrhage, which might, by an earnest searcher after al- lusions to haemophilia, be con- strued into descriptions of that disease. But I do not think that he was really acquainted with it. 104 DIAGNOSIS OF H^MOP BILIA. Chap. vii. strengthen the diagnosis ;' the absence, on the other hand, of any great haemorrhage when severe wounds have been inflicted is against the diagnosis, and es- pecially if no abundant haemorrhage have followed the taking out of a tooth ; for this operation may be looked upon as a touchstone for a bleeder. Again, if the haemorrhages have taken place from one part only, and have not been of a very long duration, the case is less likely to be haemophilia : but if the blood have come from more parts than one, and the patient have suffered from early life, while the bleedings have always lasted a long time, the case may be allowed to be placed in the lower grade of haemophilia. The foregoing remarks apply chiefly to boys. In women, haemophilia is never seen in its most intense form : in them it appears in the second or third degree, not often showing any tendency to traumatic haemor- rhages. When ecchymoses are the only haemorrhagic appearance, the diagnosis of haemophilia should not be allowed, unless the patients belong to a bleeder family : for who has not seen women in which the lightest touch does not produce extravasations of blood ? There are also certain haemorrhagic diatheses in women, which require to be distinguished from the second degree of haemophilia. The diagnosis is often a matter of difficulty : it will be treated of more fully in Chap. X., which is deyoted to the consideration of this disposition, It will be sufficient bere to remark i The presence of real hae- an hereditary disposition to bleed, mophilia must be ascertained to especially from some particular be any help to the diagnosis; for organ, is by no means uncommon. DIAGNOSIS OF HJEMOPHILIA. 105 that the diagnosis turns chiefly on the absence of the Chap. VII. diathesis before puberty, and of any predisposition to haemophilia, either in the patient's kindred or children, When a haemorrhagic diathesis appears in very young children, the question of haemophiHa may some- times be raised. Cases of umbilical haemorrhage, especially when accompanied by jaundice, often prove fatai after having shown signs of an intense haemor- rhagic disposition, the blood issuing from ali parts of the body. Cases of this kind plainly do not belong to haemophilia : they occur in children of both sexes : very rarely is any hereditary disposition present: as the great majority of the children die, there is no means of proving that in after life they are subject to haemor- rhages ; but in those, however, who survive, no tendency to haemorrhage has been remarked.' The same remarks apply to a similar disposition in somewhat older children, who, within a few days or weeks of birth, acquire an intense haemorrhagic diathesis, and at last die of the bleeding. To this class belong the often quoted case of du Gard,* and the cases of André,3 Burdach,^ Koch,^ &c. It may be remarked that haemophilia rarely causes the death of the patient before the end of the first or second year ; when death occurs earlier, the case should be viewed with suspicion, unless the patient inherit the disposition. ' Grandidier, Die freiwiUtgen * Burdach, Medie. Zeitung ( Ver- Nabelhlutungen der Neugeborenen^ eins), 1836, p. 169. Cassel, 1871, p. 85: 5 Koch, Schmidt's ^o^rW. Bd. 2 See above, p: 20. cxxxix. p. 173. 3 André, S(^vci\òi'sjahrbiichery Bd. Ixxii. p: 142. P io6 DIAGNOSIS OF HJEMOPHILIA. Chap. vii. Of the diagnosis between purpura, scurvy, and other hamorrhagic diseases on the one hand, and hamophilia on the other, it is scarcely necessary to speak. Haemo- phiUa is always congenital and persistent, while these diseases arise during the lifetime of the patient, and are usually of short duration. The sweUing of the joints, so common in haemophilìa, may readily be mistaken for some forms of rheumatism, nor are there any trustworthy means for its distinction from any other affection accompanied with a large excess of fluid in the joint. The diagnosis depends upon the circumstance of the swelling occurring in a person ai- ready known to be the subject of haemophiHa. Formerly the diagnosis was practically of more importance than at present ; for therapeutical measures, highly dangerous in the subjects of haemophilia, such as the application of leeches, &c.,were commonly resortedto for the relief of in-: flammation, With white swelling, the swelling of haemophi- lia cóuld scarcely beconfounded saveintheearliest stages : the progress of the two diseases is altogether diff'erent. The prognosis of haemophilia may be considered under two heads : during the bleeding ; iand during the absence of^bleeding. During the bleeding, the prognosis depends upon the length of time that the bleeding has lasted, and upon the amount of blood lost, together with the age and previous health of the patient. Schònlein says that the first bleeding is rarely fatai.' The bleeding seldom * Schònlein, Vorlesw^en iiher Path, u. Ther,, 1837, 3tte Auflage, Bd. ii. p. 63. PROGNOSIS OF HJSMOPHILIA. 107 stops until nearly ali the blood has left the patient's Chap. VII. body : thos|i cases in which there is one profuse haemor- rhage, which causes fainting, seem to be, on the whole, more favourable than long-continued Constant oozing. The younger the patient also, the worse the prognosis ; good general health, immediately preceding the bleeding, makes the prognosis more favourable. The kind of injury in a traumatic haemorrhage influences the prog- nosis : the bleeding after the taking out of a tooth is especially dangerous ; wounds caused by tearing and bruising are also thought to be more dangerous, Of spontaneous haemorrhages, epistaxis is the most un- favourable to the patient ; and, after that, bleedings from the bowel. Before considering the remote prognosis ofhamophilia, it will be of àdvantage to take a review of the general course and termination of the disease. Death by haemorrhage is beyond doubt the most usuai termination ; and this very early in life, few living to be 21 years old. Out of 152 boys, subjects of this disease, Grandidier found that 133 died before attaining this age.' His numbers are : During the first year there died* 20 Between i — 7 i9 61 7— H t> 36 „ 14 — 21 fi 16 „ 21 — 28 ì> 7 28—35 i> 5 35—45 i9 3 Over 50 » 4 152 » Grandidier, Schmidt's yahr- * I believe that haemophilia is biicher, Bd. cxvii. p. 333. rarely fatai during the first year: i io8 PROGNOSIS OF HJEMOPHILIA. Chap. vii. a glance at this table will show that the mortality amongst those who survive the age of 21 is somewhat less than at the ages below it : out of 71 who remained alive at 7, only 35 lived to be 14 ; while out of the 19 who lived to be 21, 13 survived to be 28 ; a difference of 50 per cent, to 70 per cent. It is possible, however, that the tendency to haemor- rhage may be lost. In one of the earliest recorded cases, by Krimer,' it is said that the disposition to bleed began to disappear between the age of 25 and 28, and Saint-Vel speaks of a case where the disposition was lost at the age of 25.* I do not feel disposed to lay much stress upon the case of the younger Thore : a boy, without any hereditary disposition, was the subject of repeated haemorrhages for the first six years of life : he then passed from observation ; but being met with again at the age of 12, it was asserted that the haemor- rhagic tendency had disappeared ever since the last observation, a swelling of the knee having taken its place.^ Bleeders are so frequently free from haemorrhage for a length of time, even years, together, especially when the joints remain swoUen, that a longer-continued observation is necessary before it can be confidently asserted that the disease has ever disappeared at this early age : it was probably a respite only, and not a at ali events symptoms rarely Hom's Archiv, 1820, Mai-Juni, p. appear before the end of the first 418. twelvemonth. The number in * Saint-Vel, Union méd,, 1865, the text is caused by the admis- t. xxvii. p. 5 16. It left behind an Sion of cases of umbilical haemor- anchylosis of the hip joint. rhage, &c. 3 Thore, Gaz. méd. . de Paris, ' Krimer, reported by Nasse, 1856, p. 653. PROGNOSIS OF HJEMOPHILIA. 109 release. Gintrac records a case where the haemorrhages Chap. VII. disappeared at 20 years of age ; but in rather more than a twelvemonth, the patient became subject to epileptic seizures, and he died during one of these attacks towards the age of 24/ Lemp also mentions a case where a man, aged 26, had remained free from haemorrhage for several years, and was enjoying excellent health at the time of observation.* In one of Grandidier's families, the father lost the disposition at about 30 years of age ; thereafter sufFered from pains in the joints and ' asthma' until 64, and died when 70 years old.^ In one of Mutzenbecher's patients the diathesis disappeared in the 37th year, but the right arm became contracted from the ' gout :'* in the 39th year, haemorrhoids appeared, and the pains in the joints became much less severe. In one of Stein- metz' cases, the patient was 65 years old, and said that for the last io years he had been free from the haemor- rhagic tendency;^ but that since that time he had sufFered from pains in the limbs, pain in the head on ^ Gintrac, Cours thèonque et clinique de Pathologie, Paris, 1853, t. iii. p. III. * Lemp, De haemophilìa nonnulla^ Diss. Inaug. Berol. 1857. P* '7' "Ex compluribus tamen annis sangninis profluvia cohibita sunt et vir nunc in aetatis anno vices- imo sexto sanitate optima fruit- ur. Il 3 Grandidier, op, cit, p. 105. A case is also mentioned (p. 30) of a man in a bleeder family who lost the tendency to bleed; but the exact age is not given : he died in his 74th year of an apo- plexy. * Mutzenbecher, quoted by Grandidier, loc, cit, Probably some form of chronic rheuma- tism. True gout is rare in Ger- many ; almost any joint afFection is called gout by the public there. 5 Steinmetz, Rust's MagazWf Bd. xxvii. Hft. li. p. 379. no PROGNOSIS OF HJEMOPHILIA. Chap. vii. one side, and heartburn. In one of Consbruch's cases, it is stated the man was then quite free from the disease ; but that he had the ' gout' worse, and that at the end of the paroxysm there appeared ecchymoses about the joint.^ The age of this patient is not given. Hughes simply States, that, on the approach of old age, the tendency to haemorrhage has been less manifest,* with- out giving any further details. Lebert's remarle, that the disease has not been seen after the age of 40,^ is disproved by numerous cases, even by one that he himself quotes/ The remote prognosis of haemophilia is indeed un- favourable. In ali cases a life of restraint must be looked forward to ; and most probably a life of suffering as well, broken only by rare intervals of something approaching to good health. The lot of these unfortu- nate persons must be very hard to be borne ; but it is not the worst, for they bave never known what it is to be well.^ Even the prognosis as regards bare existence is, until puberty has been attained and passed some years, most unfavourable : out of 152 patients, only 19 lived to be 21. There are certain circumstances which are thought ' Consbruch, Huf eland' s Jour- ^ Lafargue's. «a/, Bd. XXX. Stiick v. p. 117. ■ .. • j t ' ^ ' 5 Nessun maggior dolore, a Hughes, American Journal of ^^^ ricordarsi del tempo felice Medicai Science^ 1833, voi. xi. p. Nella miseria. tAX, Inferno^ Canto v. 3 Lebert, Arch, gén. de Mkd, But the same thought was 1837, sept. p. 56. " On n'a guère expressed long before Dante by observé d'hémorrhagie constitu- Boethius, De comol. Philos,, Lib. tionnelle après V àge de quaranta ii. Pros. iv. ans." PROGNOSIS OF HjEMOPHILIA. ih to be favourable to the patient. A patient who en- Chap. VII. joys good health between the bleedings will be more Hkely to pulì through than a feeble debilitated boy. The social position has also an* influence on the prognosis ; those belonging to the upper and middle classes have abetter chance than those of artizans. The sex is of con- siderable importance ; as the prognosis is considerably more unfavourable to boys than to girls. The prognosis will also be more unfavourable if there be complications with other diseases, as rickets, disease of the heart or nervous system. AH these circumstances, however, influence the prognosis but very slightly: the only point of much moment is the intensity of the dis- ease ; for if traumatic bleedings be absent, or only ecchymoses seen, the prognosis is much more favourable, one of the great sources of danger, the results of injury, being removed. After puberty, the prognosis is somewhat more favourable : the chance of the disposition to haemor- rhage being lost becomes a factor in it. This disap- pearance has, of ali the recorded cases, happened only g times, omitting Hughes' cases and Thore's doubtful one : so that it cannot much be relied upon. Some- thing also depends upon the trade of the patient ; if it be one where small injuries are common, the case in so many of the occupations of the lower orders, the prog- nosis will necessarily be more grave. It is not known if the prognosis be rendered more unfavourable by an hereditary transmission of haemo- philia. CHAPTER Vili. Treatment of HìEmophilia. Chap. Vili. A description of the treatment of haemophilia must necessarily be divided into several parts, corresponding to the different symptoms of the disease. The treat- ment proper to the traumatic and spontaneous haemor- rhages, and the prophylactic treatment between the haemorrhages, will be considered separately ; the man- ner, in which the swellings of the joints may be most successfuUy dealt with, wilI be described at the last. Before considering the positive therapeutics of haemo- philia, it may be well to mention those procedures which are ordinarily used in other disorders, but which cannot be employed in haemophiUa without the risk of greatly injuring the patient. First of ali, any procedure by which blood is drawn, must be absolutely avoided ; such as phlebotomy, the application of leeches, the lancing of gums for difficult teething, and scarifications of ali kinds. Then, any measures by which a loss of substance, however small, is incurred, such as the use of blisters, or of the red-hot iron, should be employed with caution. There is one case recorded of the application of blistering plaister having been foUowed by fatai haemorrhage ; and it would always be well before employing blisters to ascer- tain what results attended their use on a former occasion. The hot iron, even when employed to restrain haemor- TREA TMENT OF HJEMOPHILIA. 1 1 3 rhage, has caused a new haemorrhage at the time of the Chap. Vili, separàtion of the sloughs ; so that even this remedy must net be employed without a due consideration of the dangers which await it. The preparations of mercury seem to be particularly injurious to some cases of haemophilia ; and the physi- cian should be on bis guard when prescribing this remedy. But, on the other band, it must be remembered that mercury is usually given to bleeders with no ili effects.^ This will be the most convenient place to discuss the question of the propriety of any surgical interference with the knife. In every case on record, where ampu- tation has been done, or large artery tied, or any of the great operations of surgery performed, as, for example, lithotomy, the patient has died either of the bleeding caused by the operation itself, or of the bleeding for the relief of which the operation was undertaken : in this latter case, the wound of the operation has, in many cases, been a source of fresh haemorrhage, and thus hastened the fatai ending. With these facts in view, the question of a cutting operation becomes of the last importance. I am disposed to regard the foUowing rule as imperative : that no cutting operation be under- taken, unless the patient's life be in danger for want of that particular operation, and for which no other, not involving the use of the knife, can be substituted. The resources of conservative surgery should be strained to ^ I bave been assured tbat the foUowed by the happiest results employment of the perchloride of in the treatment of haemorrhage mercury in small doses has been in haemophilia. Q 1 14 TRE A TMENT OF HJEMOPHILIA. Chap. Vili, the utmost before any question of amputation be raised : and it is very much to be feared that Mr. MarshalPs most ingenious suggestion for performing small ampu- tations by means of the electric cautery would prove unavaiHng in practice, if the separation of the sloughs caused by the beat became a new source of bleeding. Tumours may be removed and fistulae treated by foUowing a pian lately revived by Mr. Henry Lee :' the part to be divided is gradually separated by the pressure of an elastic thread. When a stone has been detected in the bladder, a fair trial might be given to the solvent method, as carried out by Dr. Roberts :* and this would be especially adapted to children in whom urie acid calcuH are so common. In the adult, Uthotrity appears preferable to lithotomy. The removal of a tooth ought rarely to be sanctioned. Several circumstances unite to make haemorrhage from the alveolus pecuHarly uncontrollable. The divided vessels in the bone cannot fall together ; and before the bleeding can cease, they must bepluggedby athrombus, which, because the vessels cannot contract, is indisposed to form : then the warmth of the mouth, and the suction which the patient involuntarily exerts, favour the con- tinuance of the bleeding. The employment of pressure can only be partial and inadequate ; astringents can only be imperfectly applied to some parts of the bleeding surface ; this is especially true of caustics and the red- ' Henry Lee, Proceedings of the * William Roberts, A Practical Royal Med,'chir, Soc, voi. vi. p. Treatise^ on Urinary and Renai Bis- 293. Paper read June 14, 1870. eases^ London, 1865, p. 233. TREA TMENT OF H^MOPHILIA. 1 15 hot iron, which must besides lose a great deal of its beat Chap. Vili, before it can be properly got into the alveolus, unless indeed the electric cautery be used. Ali these circum- stances render the taking out , of a tooth especially dangerous ; and a great number of the fatai and alarm- ing haemorrhages on record bave been due to this trifling operation. Under these circumstances, it will be granted that a practitioner would, as a rule, be worthy of blame in allowing a tooth to be removed." i. When persons, the subjects of haemophilia, meet with an injury, it is desirable at once to use energetic measures for arresting the haemorrhage without waiting for further symptoms : the earlier the treatment is begun, the greater are the chances of success. Compression seems to ofFer the best method of resisting the bleeding; and it seems advisable to try this first before resorting to any other means. The wound should be carefuUy cleaned, any bleeding points secured, the raw surface may, or may not, be touched with nitrate of silver, and then pressure applied with a cork and buUet, or gra- duated compress. It is needless to add that many modifications of the principle of applying pressure will be suggested by various cases as they occur : they are likely enough indeed to tax the ingenuity of the surgeon to the utmost. The easy production of ecchymoses must be borne in mind, while applying- the pressure, even with a bandage, as well as the tendency to slough, In one or two cases, the compression of the artery ^ In a case recorded by Miller the gum did not cease till the ( Edinburgh Medicai Journal, 1856, tooth was taken out. Jan. p. 638^ the bleeding from 1 16 TREA TMENT OF H^MOPHILIA. Chap. Vili, leading to the injured spot has succeeded in checking the bleeding. Ligature of the artery is inadmissible : in those cases in which it has been done, death has invariably follo wed. Of styptics, Fordyce's saying stili holds good/ Ali the astringent remedies in the Materia Medica seem to have been employed. Very often many drugs bave been used without any success until the bleeding has lasted so long that it has stopped of itself. In this case a great astringent virtue is ascribed to the drug last employed. The nitrate of silver, tannin, and the per- chloride of iron seem to be the locai remedies that offer the greatest chance of success. The use of ice may be advantageously combined with compression. The hot iron is of very doubtful advantage, since when the sloughs separate, the bleeding usually begins again. Sometimes, however, it has succeeded ; and it seems proper to use it as a last resource, and where it is im- possible to use compression properly. Should a leech have been applied, and the bleeding become dangerous, it is best arrested by the use of the nitrate of Silver ; or, if this fail, as it commonly does, by the employment of a hare-lip pin and figure-of-8 suture. The haemorrhage which occurs after the removal of a tooth is very difficult to manage. The most success- ful treatment seems to be a careful plugging of the alveolus with a graduated compress soaked in the per- chloride of iron, or a thorough application of the nitrate * " Styptica qualiacumque prò nihilo erant." Fordyce, Fragmenta, p. 41. TRE A TMENT OF HJEMOPHILIA. 1 1 7 of Silver, or the electric cautery, to the interior of the Chap. Vili, alveolus, not merely touching the bleeding surface but allowing the caustic to press for a few seconds on the part as it passes over it ; this also to be foUowed by plugging.' When the bleeding has ceased, the patient must be fed on slops for several days after, as the act of mastication may easily bring on the bleeding a- gain. ii. The locai treatment of the spontaneous haemor- rhages depends chiefly on the place of bleeding, whether accessible or not. Ice may be used locally, as to the loins in haematuria, or epigastrium in haema- temesis. In epistaxis, gallic acid or tannin may be snuffed up into the nose, iced water injected, or the posterior and anterior nares plugged. Bleeding from the gums should be treated with tannin or alum washes, and ice allowed to dissolve in the mouth, while the patient is warned against sucking. In bleeding from the rectum, ice introduced within the bowel seems to be a good pian of treatment. As to the constitutional treatment of the haemorrhages : it does not in ali cases seem advisable to try immediately to check the haemorrhage when it is spontaneous, and has been preceded by symptoms of congestion, and the other prodromata described above. In these cases, if the bleedings be arrested too early, harm may be done. During the prodromata much may often be done to ward off the bleeding. The patient should be allowed only a vegetable diet, wine and meat being rigorously excluded, and two or three purgative doses given, one ' The tooth itself is used by some as a plug. ii8 TREATMENT OF H^MOPHILIA. Chap. Vili, after another. In this stage some'' bave recommended phlebotomy : the terrible danger attending its use must deter every careful practitioner from such an idea. In spontaneous baemorrhages it is well to continue the restricted diet and purgatives for some time after the bleeding has begun. The saline aperients seem to be most suitable ; for although a wider experience has not met with many examples of the surprising results de- scribed by Otto^ as obtained with the sulphate of soda, yet this salt, or the sulphate of magnesia, as recom- mended by Fordyce,^ should be preferred. ^ Consbruch, (Hufeland's^^wr- nalj Bd. xxx. Stuck v. p. 117) the warmest advocateofprophy- lactic bleeding*s, confesses that in his cases six weeks of the strong-est pressure was necessary to check the bleeding* after a little scarification : and after this the arm was swollen and blue. Wachsmuth {pp, cit, p. 51.) al- lows phlebotomy in adults only. Whatever may be the benefits of phlebotomy, the fact remains, that death has very frequently followed its employment, and the danger of this more than coun- terbalances any probable good. 2 Otto, Medicai Repository, New York, 1803, voi. vi, p. 2. "A few years since the sulphate of soda was accidentally found to be completely curative of the hemorrhages I have described. An ordinary purging dose, ad- ministered two or three days in succession, generally stopsthem; and, by a more frequent repeti- tion, is certain. of producing this effect. The cases in which the most powerful, and apparently the most appropriate remedies have been used in vain, and those in which this mode of treatment has been attended with success, are so numerous, that no doubt can exist of the efficacy of this prescription. The per- sons who are subject to this hemorrhagic idiosyncrasy, speak of it with the greatest confi- dence." 3 Fordyce, Frammenta, p. 42. The use of this remedy was sug*- gested to him by Frederick Hoff- man. TREATMENT OF H^MOP BILIA. 1 19 Should the bleeding, whether traumatic or sponta- Chap. Vili, neous, continue, it is necessary to use internai remedies with a view of checking the flow. Nearly ali the styptics of the Materia Medica have been used internally : acetate of lead, alum, the minerai acids, oil of turpentine, tannin, and gallic acid, with more or less success, or with none at ali. Small doses of tartarised antimony and ipeca- cuan have been given so as to nauseate the patient, the object being to diminish the blood pressure, and thus allow the blood to coagulate. Strychnine, kreosote, arnica, opium, and the tincture or extract of the com- mon shepherd's purse have ali been recommended. The ergot seems to have been of use in several cases of traumatic or spontaneous haemorrhages. It should be given frequently, every hour or half hour in doses of 5 to IO grains ; or the tincture may be preferred, in doses of ten to fifteen minims. It must not be forgotten that some of the patients to whom the ergot was given with such success, had already suffered great loss of blood : and it is just possible that the time of the administration of the ergot corresponded with the naturai termination of the haemorrhage. Amidst such conflicting testimony it is difficult to make out what is really the best pian to be pursued. If it could be shown that any of the drugs mentioned above had done harm to the patient, it would be certainly better to abstain from ali active interference. To do this would demand a courage which few possess : but I do not think that the patients would be thereby injured. Were I called upon to treat a case of severe haemorrhage, spontaneous or traumatic, I should prefer to use the tincture of the perchloride of iron in doses 1 20 TRE A TMENT OF H^MOPHILIA. Chap. Vili, of 30 to 40 minims every 2 hours, taking care at the same time to purge the patient with the sulphate of soda or magnesia : this last wouid of course be inap- propriate in cases of bleeding from the intestines. Did the haemorrhage continue, the ergot might beemployed, or the galHc acid, or any of the other means, as a last ' resort. When every other means has been employed, and the patient is in imminent danger of dying of loss of blood, transfusion seems to be the only refuge : it has been performed but once, in Mr. Lane's case : on the 6th day after the operation for squint, io or 12 oz. of blood were injected into the vein at the bend of the elbow : the benefit was not immediate, but in a few hours the boy, from lying as if dead, sat up and drank a glass of wine from his own band.' During the early part of a spontaneous haemorrhage, the diet, as has already been remarked, should be restricted. When, however, the patient grows weak from loss of blood, the most nourishing food that can be obtained should be given, such as the strongest beef- tea, and soups. The use of wine must be regulated by the state of the pulse. Reynell Coates* attributes the recovery of one of his patients to the generous diet, and a free use of tincture of opium : in this case it is re- mar kable that the bleeding used to stop after meals, ^ Lane, Lancet, 1840, Oct. p. gen iiber die Transfusion, in 186. Panum finds that trans- Virchow's Archiv /, path, AnaL fusion is just as efiicacious when Bd. xxvii. p. 240. whipped blood is employed, as * Reynell Coates, North Amer- when the blood is injected im- ican Medicai and Surgical Journal^ lìiediately into the veins. See 1828, voi. vi. pp. 43-45. his Experimentelle Untersuchun- TREATMENT OF HJEMOPHILIA. 121 especially after a warm breakfast. The blood apparently Chap. Vili, was drawn into the belly by the digestive fluk, leaving the external parts anaemic, and the bleeding in them being thus arrested for a short time. iii. As to the treatment between the attacks of haemor- rhage : this must be purely empirical, as the pathology of the disease is unknown. The tincture of the per- chloride of ironhas, in my experience, been of the great- est service : after its use, patients bave become less sub- ject to spontaneous bleedings, and wounds bave been foUowed by haemorrhage that was scarcely more than naturai. Mr. Christopher Heath has made the same observation.' Other preparations of ' iron do not seem to be so efficacious. With the perchloride may be given the' cod-Hver oil, if there be any wasting ; or the two may be given alternately, for six weeks at a time. From these two medicines more may be expected than from other drugs. They should not, however, be continued when there are any signs of plethora : they would then do more harm than good. Much may be done by hygienic treatment. Gold bathing is of great use, and is well borne. The patients should use a cold sponge bath every morning ; and in the summer, sea-bathing, or chalybeate baths. In England, the waters of Harrowgate may be recom- mended ; especially as the air there is dry and bracing. The patients should always be warmly clothed ; flan- nel or Scotch wool should be worn from the wrists to the ankles. They are almost always chilly, and suffer ^ Christopher Heath, British Medicai Journal^ 1868, voi. i. p. 25. R 122 TREATMENT OF HJEMOPHILIA, Chap. Vili, much from changes of temperature. Exposure to cold and damp is often foUowed by bleedings, but more frequently by swoUen joints. The diet of these patients should be nitrogenous, but unstimulating. Meat may be taken twice a day : there seems no especial reason why the white meats should be chosein ; mutton and beef, properly cooked, may be allowed. Into the diet of children, of course, milk must enter in large proportion. It would seem best altogether to forbid winej unless the patient be very weakly : it often causes inconvenient flushing of the face, even when taken in small quantity. Dequevauviller says that, in a case of Herrgott's, every time a little wine was taken a haemorrhage foUowed." Cold and damp climates and situations should be carefuUy avoided, especially when the joint swelling is a feature of the case. Against damp houses there is scarcely needed any caution. During the winter, these patients should be sent to a warm and dry climate, such as Cannes in the south of France, or Nice, Egypt or Algiers. They should leave England at the end of October, and not return till May. During the surhmer, ' Dequevauviller, De la disposi- nised that the case was not one tion aux hémorrhagieSy Thèse de of haemophilia at ali, but was Paris, 1844, No. 87. p. 36. only a temporary haemorrhagìc There is also another case which diathesis, arising during the Grandidier quotes {op, di, p. 134.) progress of whooping cough. to show the injurious effects of On the other hand, Higginbo- port wine. It is the case recorded tham found greatadvantage from by Walker in Duncan's Annals of the daily use of doublé stout Medicine f or 1797, voi. ii. p. 231, (St, Petershurger medie, Zeitschri/i, and had Grandidier seenthisorigi- Bd. xvi. p. 113.) nal, he would at once have recog- ) TRE A TMENT OF HJEMOPHILIA. 1 23 they receive great benefit from the high and dry parts Chap. Vili, of northern Scotland, where they shouid not stay after September. The advantage to be expected from a warm climate is well set forth in one of Dequevauviller's cases, where a feeble boy of 14, subject to continuai epistaxis while living in Paris, was, after two years of fruitless treatment, s'ent to Nice : in this warm and dry air the haemorrhage ceased, and the general health greatly improved. In two years he returned to Paris, and three months had scarcely gone by, when the epistaxis came back with ali the old severity. A warm climate is more imperatively demanded when thetendency to swellings of the joint is very marked ; for the swellings are commonly excited by exposure to damp and cold. iv. The treatment of the swellings of the joints must be conducted on ordinary surgical principles. During the first few days of effusion, cold or warm applications shouid be used, whichever is more grateful to the patient. Later on, after the first violence of the attack has sub- sided, the limb may be put into a splint, or cased in starch or plaster of Paris. Blisters are sometimes very useful in this stage. When the synovial fluid is but little in excess of nature, I bave seen great advantage from strapping. In prophylaxis of the joint affection, a warm and dry climate, as mentioned above, is essential. CHAPTER IX. Hygiene and Social Relations of HìEmophilia. Chap. IX. The practitioner whose duty it is to attend the fami- lies in whom this disease exists, will often be called upon to give his opinion as to the advisability of certain steps : and, in some cases, he may have it in his power to bar the entrance of so terrible a disease into pre- viously healthy families. Should the mother in a bleeder family suckle her own children ? The question has been answered in different ways by various writers who have considered the sub- ject. I do not feel inclined to attach much importance to it ; it would perhaps be safer, in those cases where it may be had, to recommend a wet nurse. The midwife should take special care that the cord is rightly tied ; and also should watch the falling off of the stunip, at which time haemorrhage is most likely to happen. Haemophilia seems to be more common among the Jews than among other races or nations of men. On medicai grounds, circumcision should certainly be for- bidden, since the danger of such an operation would be very great. I am also informed that dispensation from this ceremony can be obtained. The risk of vaccination is exceeding small : in only two cases has anything untoward ever foUowed ; in nearly ali the others, it is expressly mentioned that the HYGIENE AND SOCIAL RELATIONS OF HJEMOPHILIA. 125 vaccine vesicle ran its usuai course. Nevertheless, the Chap. IX. inoculation should be done by scarification, and not by incision, since the former seems to be less danger- ous. Those who bave charge of children, who are the sub- jects of this disease, should be admonished of the evil con- sequences that might foUow any harsh treatment of the boys. Almost every kind of bodily punishment must be forbidden. And in their occupations and amusements, great care is necessary to guard against any mis- chance. Cricket and football are plainly unsuitable. Some of the occupations of the gymnasium, and boat- ing, do not, however, seem to be hurtful. Riding may be allowed, if not foUowed by haematuria. But ali these permissions depend a good deal on the state of the joints. If the knee or ankle be very liable to swell, nearly ali these amusements must be given up, and the boys allowed to walk only, and that carefuUy. As the boys grow up, the choice of a trade or profes- sion becomes a matter of considerable importance. A- mongthe artizan class, it is difficult to choose a business in which there does not appear a likelihood of almost daily wounds. Wachsmuth recommends the occupation of an agricultural labourer ;' but this surely is as danger- ous as any other, and the exposure to the changes of weather is not likely to be favourable to the joints. In large towns, the trade of a compositor might be recommended. Among the lower middle class, the business of a clerk, either in the public services or in trade, might be chosen. For others, the ecclesiastical ^ Wachsmuth, op, cit, p. 58. 126 HYGIENE AND SOCIAL RELATIONS OF HJEMOPHILIA. Chap. IX. state,^ the profession of a schoolmaster, the law, and especially the arts, whether architecture, painting, or music, offer very suitable employments. Neither does the medicai profession seem to me unfavourable. The miHtary or naval professions must certainly be avoided. In Germany, haemophilia is a disqualification for the Landwehr. Field sports of ali kinds, except the easier kinds of fishing, should be forbidden. The recoil of the fowling piece or rifle causes large ecchymoses, and the exposure to cold and damp is unfavourable for the swellings of the joints. One very important social point is the question of marriage. Should a bleeder, or one of a bleeder family, be allowed to marry ? I think that if the person himself be a bleeder, the question of marriage ought not to be entertained. His sons may possibly escape the disease, but it is almost sure to reappear in his daughters' sons. The prospect of the certainty of so dreadful an entail of disease must repel every right thinking person from such a step, even at so great a sacrifice to himself; and it seems only necessary for the facts to be known to prevent such marriages among the better classes.* But in the case where a person belongs to a bleeder family, but is not himself the subject of the disease, ' Especially in those parts of * I say in the better classes : the Church where celibacy is for the artizan class are so ruled enforced ; for this would remove by their passions, that no moral ali prospect of transmitting* the restraints would ever be allowed disease by marriage. I do not to interfere with the gratifica- know, however, if this disease tion of a lust : the law must stop would be considered a disquali- such contracts. fìcation for Orders. HYGIENE AND SOCIAL RELATIONS OF HJEMOPHILIA, 127 should marriage be allowed ?' I think not : supposing Chap. IX. the candidate to be a man, the disease may possibly^ be passed on to his children, or grandchildren ;* and in the case of a woman, the disease is nearly certain to reappear in her sons : few circumstances with respect to haemophilia are better made out than this. The physician, whose advice is asked on this sub- ject, should be on his guard not to be deceived by any appearance of freedom from haemophilia in the women : they may seem perfectly well and free from any trace of the complaint, and yet the disease will certainly reappear in their sons. A sadder heritage of disease could scarcely be entailed : and a person enter- ing upon marriage with a knowledge of ali these facts would indeed be open to great blame. It is plain that, if haemophilia were rather more com- mon, it would afFord a good many cases of dispute in the courts of law. In Germany, it has already begun its medico-legal career, and the same may happen in this country at any moment. Should death take place from haemorrhage after a slight wound, an accus- ation of manslaughter might at once be brought ; and ^ It is surprisingf that Gran- didier should disregard the pos- sibility of haemophilia being- transmitted through the daugh- ters of bleeders : he even seems to allow of the marriage of bleed- ers themselves; and (pp, di, p. 19.) says that if a man from a bleeder family at Tenna married a woman from a healthy family, the disease did not appear in their ofiFspring. This is certainly not the case in the history of English families. « In one of Krimer's patients, the uncle was a bleeder, the father not ; yet the disease ap- peared in the sons and grandsons : See Hom's Archtv, 1820, Mai-Juni, p. 409. The case of Day (p. io.) is similar. 128 HYGIENE AND SOCIAL RELATIONS OF HJEMOPHILIA. Chap. IX. the success of the accusation would depend a great deal upon the prisoner's knowledge or ignorance on the subject of the dead man's peculiarity. If he were ignorant of the disposition to abundant haemorrhage, he could scarcely be severely punished ; while if the wound were inflicted with a full knowledge of the pro- bable consequences, the charge of murder might be substantiated. CHAPTER X. On Certain HìEmorrhagic Diatheses in Women. A chronic haemorrhagic diathesis is not unfrequently Chap. X. seen in women ; but there are few cases on record,' for those seem to bave been cbiefly cbosen for publication wbich exbibited the symptom of haematidrosis.* This ^ I have published two cases of a chronic hsemorrhagic dia- thesis in women in the Medicai Times and Gazette^ 1871, voi. ii. p. 672. * The following" are some of the most important cases : Philosophical TransactionSy 1705, voi. xxiv. No. 303, p. 21 14 (wrongly paged 2144.) Epistola Antonii Mesaporiti, M. C, Gen- uensis, ad CI. Antonium Valles- nerium. Patrick Murray, Edinburgh Medicai Essays and ObservationSy 1737, voi. ii. Art. XX. 2nd edit. p. 306. Boerhaave, in van Swieten's Comment, t. iv. § 1286. Boivin, Journal de médecine, Quoted in Dictionnaire des Sciences viéd, t. iv. p. 188. Cas rares. Caizerg-ues, Annales cliniques de Montpellier, 1814, nov. Quoted by Parrot. Chauffard, Transactions mèd. 1830, t. ii. p. 134. Gendrin, Traitk philos. de Méd. pratiqucy Paris, 1838, t. i. p. 285. Hyde Salter, Medicai Times and Gazette, 1856, voi. i. p. 253. Magnus Huss, Arch, gén, de Méd. 1857, voi. ii. p. 165. The article is also contained in full in Zeitschrift f. Min, Med, Bd. viii. p. 347; and, without the com- mentary, ìnAllgem, med, Central- Zeitung, 1856, pp. 766 and 774. Jules Parrot, Gazette hebdom. 1859, t. vi. p. 634. T. K. Chambers, Lancet, 1861, voi. i. p. 207. A. von Franque, WUrzhurger med, Zeitschrift^ 1863, Bd. iv. p. 73. Higginbotham, St^ Petershurger med, Zeitschri/Ì, 1869, Bd. xvi. p. III. There is also a case by Hoff- man, Omnia Opera, Genevae, S I30 ON CERTAIN HJEMORRHAGIC DIA THESES IN WOMEN. Chap. X, last symptom, being thought a marvel, has drawn a 'good deal of attention ; but I wish to point out that it is only part of a group of symptoms, a part of a general disposition to bleed, usually attended by indications of a grave nervous lesion. It will be seeh at once that several distinct diseases are included in the genus of chronic haemorrhagic diathesis : but sufficient attention has not yet been paid to this group of symptoms to allow any division into species to be made. i. iEtiology. In ali the cases but one, no symptoms of haemorrhage appeared before puberty. In Parrot's case the haemorrhages appeared about the age of 6 years : under the influence of anger, the tears were coloured with blood, and blood also appeared at various parts of the skin. In Boerhaave's case, which is the next earliest, symptoms appeared in the twelfth year, with the first menstruation. Boivin's case gives the latest age ; for the woman was perfectly well up to the 28th year of her life. In most of the cases, nothing is said of the previous habits and constitution of the patient. In 4 cases it is stated that the general health was very good up to time of the setting in of the diathesis. In three cases it is stated that the patients were of an irritable disposition. 1740, t. iii. sect. i. cap. V. p. 63; only temporary haemorrhag-ic and by Stahl, De vns mensium diathesis, or are too meagre in tnsoL cap. v. ; and by Le Cat, detail to be serviceable. There Journal de mèdectne, 1764, t xx, are also many cases quoted by avril, p. 326, and a namber of Latour, Histoire philos, et méd, des cases arq referred to by Haller, Hémorrhagies^ Paris, 1828, t, i. p. Elem, Phys, lib. xxviii. § iii. p. 226. 157; but most of them are either ON CERTAIN HJSMORRHAGIC DIATHESES IN WOMEN. 131 In seven of these cases, the first haemorrhage was Chap. X. preceded by a violent moral emotion, which, in four cases, was brought about by some external injury. In two, the haemorrhages first appeared while the cata- menia were flowing. ii. Symptoms. In 5 cases, the exciting cause of the haemorrhages could be traced to mental emotion. In Huss' case, the patient could even bring them on at will, by firmly directing her attention to the part. In my own two cases, the patients told me that they had never observed haemorrhage to follow mental emotion. Traumatic haemorrhages bave only been noticed in Higginbotham's and my own two cases. In Hyde Salter's and Huss* cases, spontaneous, and sometimes traumatic, ecchymoses were noticed. In Huss' and Patrick Murray's, wounds were not foUowed by ex- cessive bleeding ; but in ali the other cases nothing is said on the subject. The spontaneous haemorrhages may come fi:"om ali parts of the body ; the mucous membranes, or skin ; and in the latter case, the name of haematidrosis is given to the symptoms.^ The bleedings may occur from nearly every mucous membrane ; the nose, the mouth, and the uterus are the most common sources of blood ; rarely is haematuria seen. Very often the haemorrhage ^ I am compelled to treat the known of this phaenomenon the subject of haematidrosis super- reader must consult Gendrin's ficially : the limits of this work Traitè philosophique de Médecine will not allow as full a discussion pratique, Paris, 1838, t. i. p. 276; of this symptom as its interest and Jules Parrot's articles in the demands; and for a philosophi- Gaz, hebd. for 1859, beginning at cai account of nearly ali that is p. 633. 132 ON CERTAIN HJEMORRHAGIC DIATHESES IN WOMEN. Chap. X. chiefly occurs from only two points ; such as the nose and uterus ; or the stomach and the skin. Bleeding may take place from any part of the skin : in Boivin's case it is said that there was no part of the skin which had not yielded blood. In the others the blood has issued from parts of the skin which are the most thin and delicate, and which pers- pire more readily ; thus bleedings bave been most frequently seen from the face, the neck, the axillae, the front of the chest, the inside of the thighs and arms, and the skin by the sides of the nails. Sometìmes the blood Comes from the eyelids, conjunctivae, and ears ; or from the hands and feet ; or from the hairy scalp. The skin from which the blood flows is usually quite naturai ; and when the haemorrhage has ceased, no traces are left behind. In most of the cases, a pruritus and hyperaemia, together with some swelling and slight sense of pain, precede the flow of blood. Huss exam- ined the bleeding surface of the scalp with the aid of a lens, and found the blood arise around the root of each hair, and form a little point of blood through the cen- tre of which the hair passed : this point increased, and became a drop, which, uniting with other drops simil- arly formed, ran off. Observers are agreed that the blood escapes in other parts, which are free from hairs, from the orifices of the sweat glands ; and Parrot thinks that in ali cases the flow of blood takes place from the sweat glands only. The fluid which escapes from the skin contains red corpuscles : this fact has been determined by Huss, Chambers, Parrot, and von Franque. In Chambers' case the blood from the skin did not form rouleaux, ON CERTAIN HJEMORRHAGIC DIATHESES IN WOMEN, 133 while that from the finger did so quite naturally. Huss Chap. X. found in the blood from the scalp no alteration of the red corpuscles in shape, but they did not forni rouleaux; there was a complete absence of the white. The blood was always of a bright red colour, like arterial blood. In Patrick Murray's old case, the blood was no higher coloured, nor of thicker consistence than water in which flesh has been washed. In Murray's and Higginbotham's cases, the quantity of blood lost was fabulous. In the first case, half a pound of blood was lost from the nose every day for two years, exclusive of what was lost from the uterus, stomach, and the skin. In the second, menorrhagia lasted 472 days, the patient losing half a pound of blood daily ; so that, altogether, 2800 to 3000 ounces must bave been voided. As a rule, the amount of blood lost, although considerable, is not nearly so great as this ; enough is lost, however, to cause great anaemia. The presence or absence of menstruation seems to bave no influence on the disease. Out of the 13 cases, the references to which I bave given in the note to p. 129, the menses remained unaltered in 6; they were irregular, sometimes profuse, sometimes absent, in 2 ; their appearance several times is mentioned in 2 cases, but no further details given ; in only one case were they entirely absent ; and in the remaining two, there was menorrhagia. In my own two cases, menorrhagia was a prominent symptom. In 7 cases, in which the haematidrosis was the most prominent symptom, there bave been nervous attacks about the nature of which considerable doubt is usually 134 ON CERTAIN HJEMORRHAGIC DIATHESES IN WOMEN, Chap. X. expressed. They are looked upon as either epileptic or hysterical. In ali the cases, except Chambers', there appear to bave been general convulsions. In Parrot's case, the patient became almost maniacal. In von Franque's case, the disease was thought, by some of the physicians who saw the patient, to be chorea. iii. Duration. In 8 out of the 13 cases, the dis- ease was in progress at the time that the authors wrote their description. In Gendrin's case, the patient married, became pregnant, and lost ber troubles ; but the haemorrhagic diathesis in this case was not very pronounced. In Higginbotham's case it is not quite certain if the patient recovered or not. In the other three cases, the symptoms had disappeared. In my own two cases, the disease had lasted certainly 12 years in one case, and 4 in the other. The disease does not seem to bave any influence in shortening life : in Boivin's and Murray's cases, where great quantities of blood were daily lost, the patient continued to live many years. iv. Pathology. I am not aware of any records of a post mortem examination of a patient suffering from a haemorrhagic diathesis of this kind. There seems to be no appreciable disease of the blood : it is not want- ing in fibrin, for it coagulates quickly and firmly ; nor are the corpuscles altered. It does not seem to be any way related to menstruation, since in many of the cases, the catamenia remain unaltered throughout the progress of the malady. It is a matter of almost daily observation that women are far more liable than men to spontaneous haemor- rhages of ali kinds. In women, a spontaneous haemor- ON CERTAIN HJSMORRHAGIC DIA THE SE S IN WOMEN. 135 rhage is a naturai phaenomenon every month ; and at Chap. X. every catamenial period, there appears to be a greater disposition in other parts of the body, remote from the uterus, to bleed upon sHght causes : in many of the cases of haemorrhagic diathesis, the bleedings bave first occurred at the monthly period.^ In many of these cases, the exciting cause, not only of single haemorrbages, but even of the haemorrhagic diathesis, appears to bave been a violent mental emo- tion ; in some of them, again, coinciding with the flow of the catamenia. That a temporary haemorrhagic diathesis may be caused by mental emotion is shown by the observation of Lordat : a woman of bad life, and extremely irascible character, was seized by the police and taken to prison. She became furiously angry ; and shortly after, sufFered a haemorrhage from the nose and mouth ; and an eruption of purpuric spots, which covered the whole body ; the largest of these spots were an inch in diameter.* In women, the emotions are under little control : diseases, caused by the emotions, as hysteria, are common : and there is good reason, in the cases mentioned above, for the be- lief that the haemorrhagic diathesis was established as sequence to the violent moral emotion. In other cases, the symptoms bave been complicated by the appear- ance of nervous phaenomena, general convulsions ; * The reader will find the re- quoted, by Severinus and Flor- ferences to many of these cases entinus Leudanus, of two nuns, in Jules Parrot's last article. who, being by chance greatly * Lordat, Tratte des hémorragies, alarmed, suffered an exudation Paris, 1808, p. 84. There are of blood from the skin and other also two old cases, frequently parts. 136 ON CERTAIN H2EMORRHAGIC DIATHESES IN WOMEN. Chap. X. SO that it does not seem impossible that the disease may arise from some lesion of the centrai nervous sys- tem, implicating as well the vaso-motor nerves, the paralysis of which may be the cause of thè haemor- rhages, by relaxing the walls of the blood vessels, and thus allowing their rupture by an amount of blood pres- sure far less than in the naturai state. In some cases, the haemorrhage is limited to one side of the body. Haematidrosis is but a part of the symptoms of a haemorrhagic diathesis. In ali the cases in which this bloody sweat has occurred, except ChaufFard's, haemor- rhage, usually abundant, has also occurred from the mucous membranes as well. V. Diagnosis. At first sight, the diagnosis may not be easy. The resemblance to haemophilia may be very great : in my own two cases, it was almost com- plete. In making the diagnosis, the hereditary and congenital character of haemophilia must be kept in mind ; if no symptoms of a disposition to haemorrhage bave appeared until after puberty, the case cannot be one of haemophilia : further, the rejection of the dia- gnosis of haemophilia will be strengthened, if there be no trace of the presence of this disease in the kinsmen : and especially if the women bave borne sons, free from haemophilia ; haemophilia being nearly sure to reappear in the sons of a woman, who is herself the subject of haemophilia. If, on the contrary, the women spring of a bleeder family, with symptoms appearing in child- hood, the case must clearly be referred to haemophi- lia. Haemophilia is almost the only disease with which these haemorrhagic diatheses could be confounded. ON CERTAIN HJEMORRHAGIC DIATHESES IN WOMEN. 137 The acute haemorrhagic diatheses are excluded by the Chap. X. short course which they run. The haemorrhagic dia- thesis of leucaemia will be recognised by the increase of leucocytes in the blood, and the enlargement of the spleen or lymphatic glands. vi. Treatment seems to bave little influence over the haemorrhagic diathesis. In most of the cases, the drugs employed seem to bave in no way influenced the course of the disease. In my own two cases there was certainly some relief from the locai symptoms after the employment of large doses of the tincture of the per- chloride of iron. A fair trial might also be given to the secale cornutum and oil of turpentine. For the alleviation of the nervous symptoms, opium or chloral may be given in moderate doses ; but care must be exercised in their administration, as the pa- tients are very likely to acquire a habit of employing these remedies in excess. The inhalation of chloroform vapour seems to be of great use in checking the con- vulsions, which must, of course, be distressing to the bystanders. CHAPTER XL LlTERATURE OF H^EMOPHILIA. Chap. XI. Haemophilia is shortly described in the text books by Erichsen, Miller, Tanner, Holmes, Wood, Austin Flint, Gross, Rilliet and Barthez, Bouchut, Griselle, FoUin, Monneret, Gintrac, Schònlein, Canstatt, v. Pitha and Billroth, Felix v. Niemeyer, &c. The de- scriptions are none of them complete. There is a good account of the disease by Virchow in the first volume of bis Handbuch. The following monographs bave also appeared : James Miller, Monthly Journal, 1842, July, p. 567. This paper deals chiefly with the treatment. Nasse, Correspondenzblati rheimsch-westphàL Aerzte, 1845. ^o. 14. Schneider, Henke's Zeitschrift f, d, Staatsarzneik,y 1847, ^d- 1^^^- p. I. L.a,nge, Medidm'scAe Zeitung (Vereins), 1847, p. 124. Ueber geo- graphische Verbreitung der Bluterkrankheit. Lange, Oppenheim's Zeitschrift, 1851, Bd. xlv. p. 145. Wachsmuth, Die Bluterkrankheit, Magdeburg, 1849: this first appeared in Zeitschrift des deutschen Chirurgenvereins, Bd. iii. p. 459. Bordmann, De l'hémophilie, Thèse présentée a la Faculté de Méd- ecine de Strasbourg, 1851. Grandidier, Die Hàmophilie oder die Bluterkrankheit, Leipzig, 1855. Grandidier, Schmidt's yahrbiìcher, Bd. cxvii. p. 329. Bericht ueber die Hàmophilie. Laycock, Medicai Times and Gazette, 1862, voi. i. p. 500. LITERATURE OF HJEMOPHILIA. 139 The foUowing cases have been arranged in alphabet- Chap. XI. ical order, in geographical classes. Cases of mere haemoiThagic diathesis have been rejected, whether of umbilical haemorrhage, as the cases of Minot, Bow- ditch, Manley, Dubois, Mende, Beckhaus, &c., or of pseudo-haemophilia, as those of Huss, Higginbotham, and some others. Cases, again, of a great haemor- rhage on one occasion only, have been omitted, such as those of Droste, Sturm, &c. Many cases, hitherto un- noticed, have been added to the list. American. W. and S. Buel, ^ Transactions of the Physico- Medicai Society of New Fbrk, 1817, voi. i. : also in the London Medicai and Physical Journal, voi. xl. p. 429 ; ^Hamburger Magazin fUr die ausi. Ut, Bd. iii. p. 449; ^Gott, gel. Anz, 182 1, Stùck xcii. ; ^Journal universel des sciettces méd, t. xiii. p. 349. Reynell Coates, North American Medicai and Surgical Journal, Phila- delphia, 1828, voi. vi. p. 37: also in Kleinert's Repertorium, 183 1, Heft. xi. p. 54; ^Sammlung auser. Abhandl, f prakt, Aerzte, Bd. xxxvii. ;• ^Journal des Progrh, t. xiii. p. 61. Gould, Boston. Medicai and Surgical J oumal, 1857, voi. Ivi. p. 500; also in Medicai Times and Gazette, 1858, voi. ì. p. 19. Only the ge- nealogical tree of a certain family. Hay, New England Journal of Medicine and Surgery, Boston, 1813, voi. iì. ^, 2,2,\\ also in London Medicai Repository, 18 15, voi. iii. p. 69; Meckers Archivfd, Phys, 1816, Bd. ii. p. 138; ^Hufeland's Journal, Bd. xli. Stuck iii. ; *^ Journal general, t. Iv. p. 418. J. N. Hughes, * Transylvania Journal of Medicine, voli. iv. and v. ; also in American J oumal of Medicai Science, 1833, voi. xi. p. 54^* * The references marked with an asterisk are those which I have not myself verìfied. ..» 1 40 LITERA TURE OF HJEMOPHILIA. Chap. Yl,Archives gén. de Mèdectney 1833, oct. p. 278;^ *Frorìep's Notizen^ 1838, Nr. 135. Otto, Medicai Repository^ New York, 1803, voi. vi. p. i : also in London Medicai and Physical Joumaly voi. xx. p. 69; London Medicai and Chtrurgtcal RevteWy voi. x. p. Ivii. ; Meckers Arch,/, d, Phys, 18 16, Bd. ii. p. 138; Dictionnaire des Sciences mtdicales^ t. iv. p. 190; ^Gdit. gel, Anz, 1806, and 1809; ^Annales de littérature méd, ètranghrey t. vii. p. 163. The history is continued in the Philadelphia Medicai Mu- seuniy 1805, voi. i. p. 286. Tranéus, ^-SV. Louis Medicai and SurgiccU Journal^ 1870, p. S3S • also in Virchow and ìlirsch! s Jahresbericht /. 1870, Bd. ii. p. 286. E. H. Smith, Philadelphia Medicai Museum, 1805, voi. i. p. 284 : a letter from Dr. E. H. Smith, of New York, to Benjamin Rush, M.D. dated Aprii 9, 1794 : at p. 288, the editor, Dr. J. R. Coxe, quotes 3 cases from Lowthorp's Ahrìdgment of ihe Philosophical Transacttans : also in Sammlung auserlesener Abhandl, f, p, Aerzte, Bd. xxii. p. 269. Belgian. Benavente, ^Annales de la Sociéié de Méd, d'Anvers, 1861, avril- mai: also in CdiTisisXM ^ Jahreshericht /, 1861, Bd. iv. p. 230. Gobée, ^Oppenheim's Zeitschri/t, Bd. xxvii. Danish. P. St. Ursìng-, ^Journal /or Medicin og Chirurgie : also in Kleìn- ert's Repertorium, 1838, Aprii, p. 25 ; "^Med, Annoi, der hadischen Sani-- tàlscomm.y 1837, Bd. iii. Heft. iii. DUTCH. Tamme Beth, ^Specimen med, inaug, exhihens historiam haemorrhagiae insólitae e digitis dextrae manus et simul hereditariae, Groning. 1829. Donkersloot, Nederlandsch Lancety 1850;, p. 416. X In the Archives gén,y the name way of spelling has been followed by Hughes has been changed into Hugues, the Germans, Virchow only èxcepted. apparently owing to the radicai incapa- {Handh, d, spec. Patf^ «. Ther. Bd. i. bility of spelling a foreigner's name p. 264.) correctly, that the French possess : this Hr* LITERATURE OF HJEMOPHILIA. 141 East Indian. Chap. XI. Heymann, Archiv /. path. Anat, Bd. xvi. p. 182: also in ^Allgem, med. Central' Zeitungf 1859, Nr. 42. A Mohammedan family at Pa- lembang, in Java. English, Allan, Monihly J oumal, 1842, June, p. 501 : also in ^Archives gén, de Méd, 1843, 4« sèrie, t. i. p. 83. Babington, Lancet, 1865, voi. ii. p. 362 : also in Centrali),/, d, med. Wùs, 1865, p. 864. Cases of hereditary epistaxis. Blag-den, Med.-chir. Trans. ^ voi. viii. p. 224. Burns, Lancet, 1840, Dee. p. 404. Buss, Medicai Times and Gazette, 1868, voi. ii. p. 530. Clay, Medicai Times, 1846, Jan. io, p. 293 : also in ^Prager Vier- teljahrschrifty 1847, Bd. iii. ; ^S^^vcìxàs!^ Jahrhiicher, 1847; *Oppen- heim's Zeitschri/t, Bd. xxxiii ; Gaz. mèd., 1846, p. 568. Clutterbuck, Lancet, 1826, Aprii, p. 99. Cochrane, ihid. 1842, Aprii, p. 147: also in ^Hufeland's Journal, Bd. xcv. Stiick vi. ; *Canstatt's Jahreshericht, 1842. After quoting several cases of obstinate hsemorrhage, describes the case of a man who nearly bled to death after the taking out of a tooth. The case of Walker, in Duncan's Annals of Medicine for 1797, voi. ii. p. 231, is one of a haemorrhagic diathesis coming on and disappearing dur- ing an attack of whooping cough. Cousins, Medicai Times and Gazette, 1869, voi. il p. 277: also in Virchow and ìlirsch^s Jahreshericht fUr 1869, Bd. ii. p. 269; Or B.\g, Edinburgh Journal 0/ Medicai Science, 1826, voi. ii. p. 64: quoted also by Cochrane, who gives quite a wrong impression. Three cases are related, one only has any likelihood of belonging to the class of haemorrhagic diathesis. Davis, Edinburgh Medicai and Surgical Journal, 1826, voi. xxv. p. 291: also in *Horn's -4rr^/z/, 1826, Mai; **Froriep's Notizen, 1826; ^Med. chirurg. Zeitung, 1826, Bd. iv. Druitt, Provincial Medicai and Surgical Journal, 1845, Aprii, p. 260. Durham, Guy' s Hospital Reports, 1868, voi. xiii. p. 489: also in Virchow and ì^\r%ch! s Jahreshericht fUr 1868, Bd. ii. p. 275. 142 LITERATURE OF H^MOPHILIA. Chap. XI. Fordyce, Fragmenta chirurgica et medica^ Lond. 1784, p. 41 : also in "^ ^Sammlung auser, Abh, Bd. xi. Hay, Monthly Journal, 1842, p. 264. Christopher Heath, British Medicai Journal, 1868, voi. i. p. 25 : also in Virchow and Hirsch's Jahreshericht far 1868, Bd. ii. p. 275 : and Schmidt's/d!^r33. Bd. cxxxix. p. 172. Hooper, reported by Burns, Lancet, 1840, Dee. p. 405. Hunt, Provincial Medicai Journal, 1842, May, p. 143 : also in *Can- stdXt's Jahreshericht, 1843, Bd. iv. Kendrick, London Medicai Gazette, 1830, p. 788. This case was described afterwards by Liston. Lane, Lancet, 1840, Oct. p. 185 : also in ^Arch, gtn, de Méd, 1841, févr. p. 234; *Froriep's Notizen, 1841, Nr. 394; *Canstatt's Jahres- hericht fUr 1841, Bd. i. ; *Kleinert's Repertorium, 1841 ; *Oppen- heim's Zeitschrift, Bd. xxxvi. p. 581. Wickham Legg-, St, Bartholomew* s Hospital Reports, 1 87 1 , voi. vii. p. 23. Liston, Lancet, 1839, Aprii, p. 137: also in **Hufeland*s /^«/Tztz/, Bd. Ixxxviii. Stiick iv. p. 184. London Medicai and Physical J oumal, voi. xl. p. 431. Marshall, Medicai Times and Gazette, 1870, voi. ii. p. 728. John R. Miller, Edinburgh Medicai Journal, 1856, Jan. p. 638. Alexander Murray, Edinburgh Medicai and Surgical Journal, 1 826, voi. xxvi. p. 33. OshornQ, Duhlin y oumal 0/ Medicai Science, 1835, voi. vii. p. 32: also in **Arch, gèn, 1835, juli, p. 385 ; **Hamh, Magazin, Bd. xxx. p. 131; ^^Yrone^'^ Notizen, 1835, Oct. Hyde Salter, Med, Times and Gazette, 1856, March, p. 253 ; also in ^Cdi.nsXBXt^& Jahreshericht /ur 1856, Bd. iv. The history of a woman with a haemorrhagic diathesis is recorded, and a family of bleed- ers spoken of. Smethurst, Lancet^ 1841, Jan. p. 648. Two cases of a haemor- rhag-ic diathesis in women. Taynton, London Medicai Gazette, 1836, Jan. p. 659; also in *Froriep's Notizen, Bd. xlvii. Nr. 1036. Wardrop, On Blood letting, London, 1835, p. 13. Ward, ibid, p. 16. Waterhouse, British Medicai Journal, 1870, voi. i. p. 128, and voi. ii. p. 679. LITERATURE OF HJEMOP HILIA. 143 West, Provinctal Medicai Journal, 1842, Sept. p. 438. Chap. XI. Wilmot, Dublin Journal of Medicai Science, 1841, voi. xix. p. 234 \ also in ^London Medicai Review, 1841 ; ^Oppenheim's Zeitschrift, Bd. xix. p. 431, James Wilson, Lectures on the Blood, &c., London, 1819, p. 410. James A. Wilson, M.D., reported by Lane, Lancet, 1840, Oct. p. 187. French. Bérard, quoted by Canstatt, Handh, der med, Klinik, 1843, B^» i» P» 139. Castan, ^Montpellier medicai, 1869, octobre: also in Lyon medicai, 1869, ^' "^' P* 4^4- Crasner, Gazette medicale de Paris, t. iv. p. 599. Delmas, ** Journal de Méd. de Bordeaux, 1868, oct. p. 455 : also in Virchow and IHirscì)! s Jahreshericht Jur 1868, Bd. ii. p. 275. Dequevauviller, De la disposition aux hémorrhagies, etc. Thèse de Paris, 1844, No. 87 : also in ** Journal de Chirurgo par Malgaigne, 1844, juin, p. 164. Eight cases are recorded : only 3 are haemo- philia. De Fleury, Mémoires de la Société méd, chir, de Bordeaux, 1866, t. i. p. 299. Fournier, Ga&ette des Hòpitaux, 1851, p. 493 : also in *Canstatt*s JahresherichtJ. 185 1, Bd. iv. p. 169. Gavoy : see German cases. i Gintrac, Cours théorique et clinique de Pathologie, Paris, 1853, t. iii. p. I IO : also in Mémoires de la Société méd, -chir, de Bordeaux, 1866, t. i. p. 312. Guépratte, ** Journal des connaiss. méd, -chir, 1844, juin: also in CdLXìsXdXi's Jahresbericht JUr 1844, Bd. iii. p. 291. Laborie, Gaz, des Hòp, 1835, t. x. p. 178. This case is the same as that recorded by Lafargue. Lafargue, Revue méd. 1835, t. iv. p. 89: also in "^Joum, hehdom, des progrh, 1835, aoùt; Gaz, des Hop, 1835, t. ix. p. 410 ; <*Schmidt's I Since Germany has resumed the possession of Alsatia, I have thought it right to place the cases from Strassburg among the German observations. 144 LITERATURE OF HJEMOPHILIA. Chap. Yl,Jahrbh. 1835, p. 57; *Oppenheim.'s Zeitschrift, Bd. i. p. 106; *Fro- riep's Notizen, 1835, Nr. 99. Laveran, Gaz, hehdom, 1857, p. 621. Under the name of hsemo- philia, a case of leucsemia with abundant epistcìxis is described. Lebert, Archwes gèn. de Méd, 1837, sept. p. 36: also in Med. Chir, Review, 1838, July, p. 226; ^Froriep's Notmn, 1838, Nr. 119 and 120. Only 2 out of the 16 cases are new. Poncet, Lyon méd, 1871, t. viii. pp. 785 and 798. Victor Resal, Quelques pages sur VMmophylie, Thèse de Paris, 1861 : also in Canstatt's Jahreshericht /, 1861, Bd. iv. p. 228. Three cases of haemophilia limited to spontaneous hsemorrhage. Ritgen : see German cases. Roux, *^ Journal de Méd, et de Chir, prat,, 1833, voi. viii. Quoted also by Lebert. Saint Vel, Union méd, 1865, p. no: also in Csxi^idXt! ^ Jahreshericht /, 1865, Bd. iv. p. 125 ; Schmìàt^&yahrbb, Bd. cxxx. p. 27. Schnepf, Gaz, mèd, de Paris y 1855, p. 671. Sentex, Mtmoires de la Sociétè méd,'chir, de Bordeaux, 1866, t. i. p. Tardieu, Archives gén, de Méd, 1841, févr. p. 185 1 also in ^Oppen- heim's Zeitschrijt, Bd. xvii. Heft. iii. p. 367 ; ^Schmidt's Jahrhb, Bd. xliii. Thore, Gaz, méd, de Paris, 1856, p. 653 : also in Schmidt's Jahrhb, Bd. xciv. p. 186. WolfF: see German cases. German. Abt, ^Oesterr, Zeitschrift Jur prakt, Heilkunde, 1855, Juni. Assmann, Die Hàmophilie, Diss. Inaug-. Berol. 1869: an abstract in Virchow \màli\rsch's Jahreshericht J, 1869, Bd. ii. p. 268. Beier, De haemophilia, Diss. Inaug*. Berol. 1864: an abstract in Cbxì%\.bXì' s Jahreshericht J. 1864, Bd. iv. p. 158. Besserer, ^ Correspondenzhlatt rhein,-westph, Aerzte, 1845, Dee. : also in CdJisXBXt! ^ Jahreshericht Jur 1845, Bd. ii. p. 29. Bicking, YhiieÌBXià'^ Journal, Bd. Ixxxiv. Stuck iv. p. no. V. Bippen, ^Bericht iiher die Vers, der Aerzte u, Naturjorscher in Mcdnz, 1843, und in Bremen 1844: quoted also by Heyland, ^Neue med, chir. LITERATURE OF HJEMOPHILIA. 145 Zettungf 1844, Nn 5 ; also in ^Gaz. mid. de Strasbourg ^ 1843, P- Chap. XI. 408. Qaudi, Oesterr, med, Wochenschn/Ì, 1841, Nr. 19, p. 435. Conradi, ^De morbo maculoso haemorrhagico, Diss. Inaug. Gòtting. 1829. Consbruch, Hufeland's Journal^ Bd. xxx. Stuck v. p. 1 16 : also in Journal gén. de Md. Paris, 181 1, t. xli. p. 115; ^Bzbl. méd. t. xxxiii. p. 392; ^Annales de liti, méd, ètrang, t. xiv. p. 313. Cramer, Caspar's Wochenschn/t, 1835, p. 529. Elsàsser, Hufeland's Journal^ Bd. Iviii. Stiick v. p. 89; Bd. lix. Stiick iii. p. 109; Bd. Ixvii. Stiick v. p. 122 ; Bd. Ixxvii. Stuck v. p. 133 : also in Edinburgh Medicai and Surgical Joumaly 1826, voi. xxv. p. 454 ; ^ Noisette Ubi, mkd. t vii. p. 487 ; ^Bull, des Sciences méd, U »ij- P- 353- Erdmann, ^Diss. de haemophilia^ Hai. 1844. Escherich, ^Wurtemb, med, Correspondenzblatt^ 1835, Bd. v. Nr. 19; also in Henke's Zeitschnfì f. d, Staatsartneikunde^ 1847, Bd. liii. p. 18 ; Schmidt'syiz^r^^. Bd. xiv. p. 25. Finger, ^Oesterr, Zeitschrift f, pràkt, Heilk, 1859, Bd. v. : also in Schmidt's J^a^r^^. Bd. cvii. p. 301 ; Bd. cxvii. p. 330. Fischer, ^Zeitschri/t /, Chirurgie u, Geburtsh, 1855, Bd. i.; also in Schmidt'sya^r^^. Bd. Ixxxvii. p. 136. Frànzel, Medicinische Zeitung (Vereins)j 1833, p. 164, Gavoy, ^ JO hèmopkiHe ou diathèse htmorrhagique^ Thèse de Stras- bourg, 1861 : also in Cdjìs^tdXt^s, Jahresbericht, /, 1862, Bd. iv. p. 155. Grandidier, ^Allgem, med. Zeitung y 1837, Nr. 69. Grandidier, ^Holscher's Annalen, 1839, ^^* ^v. : also in Schmidt's Jahrbb, Bd. xxviii. p. 170. The same family is also described in his ^De Disp, adhaemorrh, lethaVhereditaria, Casselis, 1832, Gròschner, Rust's Magazin, Bd. xxxvi. p. 397. Henschel, Schmidt's ^bi^r^A Bd. cxvii. p. 331. Heyfelder, Medicinische Zeitung (Vereins), 1833, p. 215. Hopf, ^Die HàmophiHcy Wiirzburg, 1828. Johannsen, ^Diss, de Haemorrhaphiliay Kil. 1842. Jungken, Deutsche Klinik, 1849, P* 55* Kerksig, ^ Sanitàtsbericht der westphàl. Med, Coli,/. 1843, p. 80. Krimer, reported by Nasse, Hom's Archivy 1820, Mai-Juni, p, 409. V 146 LITERATURE OF HJEMOPHILIA. Chap. XI. Kuhl, ^ Opuscula medica, quaest, chirurg,, 1834, pars xiii. : also in *>Clarus und Radius Bettràge, 1836, Bd. ii. Kiister, Caspar's Wochenschri/i, 1847, p. 282. Lange, Medicinische Zeiiung ( FereznsJ, 1846, p. 24. Lemp, De haemophilia nonnulla, Diss. inaug. BeroL, 1857: also in Schmidt's Jahrhh, Bd. cxvii. p. 330. Lòwe, Zeitschrift des deutschen Chirurgenoereins, Bd. i. p. 685. Lucas, ^ Sanitàtsberìcht des rhetn, Med, Coli. /. 1835 : also in Fro- riep's Notizen, 1838, Nr. 121, p. 175. Martin, ^Jenaische Annalen, 1851, Bd. ix. p. 307. ** Medicinische Ephemeriden, Chemnitz, 1793, p. 267: also in GÒtt, gel, Ann, 1794, p. 279. Medicinische Zeiiung (Vereins), 1835, p. 27. Meinel, ^/enaische Annalen, 1851, Bd. ix. p. 298. Melicher, Oesterr, medie, Wochenschrift, 1844, Nr. 32, p. 869. Miling, Medicinische Zeitung (Vereins), 1844, p. 31. Mùller, ^De Morhis maculos, haemorrh,, Gòtt., 1829. Miiller, J. J. Schmidt, ^ De haemorrhoea, Erlang. 1829. Mutzenbecher, ''^Diss, de haemorrhagicis, Heidelberg, 1841. Nasse, Horn's Archiv, 1820, Mai-Juni, p. 385. Otte, Ueber die Bluterkrankheit, Leipzig, 1865 : a reproduction of an inaugurai Dissertation at Bonn in 1863 : also in Schmidt's Jahrbh, Bd. cxxx. p. 25, Quadrat, Oesterr, med, Wochenschri/t, 1841, Nr. 33, p. 769. Two cases of doubtful haemophilia. Rave, ^ Beohachtungen und SchlUsse aus der praktischen AmneTwissen- schaft, 1798, Theil ii. p. 13.^ Reinert, Ueber Hàmophilie, Diss. Inaug. Gòttingen, 1869, Rieken, Neu^ Untersuchungen in Betreff der erhlichen Neigung zu lodi- lichen Blulungen, Frankfurt, a.M. 1829: also in ^Annales de la SociéU de Med, d'Anvers : ^Bullel, de Thèrapeutique, t. xviii. p. 388* Ritgen, *(r^. mkd, de Strasbourg, 1843, P- 40^« Ròsch, * Untersuchungen aus dem Gebiete der Heilwissenschaft, Stuttg. 1837, Bd. i. p. 249. z Grandidier says that this case has referred to by S. G. Vogel in his Handb. not been mentioned, with reference to der proci, Arzneywissenscha/tt Theil v. p. haemophilia, before the publication of 14. after the cases from the Af^ SS. 107. LONDON ' PRINTBD BY H. K. LEWIS» GOWER STREET Btòf FUBLISHED AND SOLD BT H. K. LEW^IS, 136 GOW^ER STREET, W^.C. A Guide to the Exàmination of the Urine; intended chiefly for Clinical Clerks and Students. By Dr. J. Wickham Legg. Third Edition, Revised, In the Press. A Text Book of Practical Medi- cine, with particular reference to Physìology and Pathological Anatomy. By Felix von NiEMEYER. 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